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Sample records for anticancer quinolone derivative

  1. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

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    Rachael E Hawtin

    Full Text Available BACKGROUND: Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research. METHODS/PRINCIPAL FINDINGS: Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more

  2. Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia.

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    Jamieson, Gene C; Fox, Judith A; Poi, Ming; Strickland, Stephen A

    2016-09-01

    Vosaroxin is a first-in-class anticancer quinolone derivative that targets topoisomerase II and induces site-selective double-strand breaks in DNA, leading to tumor cell apoptosis. Vosaroxin has chemical and pharmacologic characteristics distinct from other topoisomerase II inhibitors due to its quinolone scaffold. The efficacy and safety of vosaroxin in combination with cytarabine were evaluated in patients with relapsed/refractory acute myeloid leukemia (AML) in a phase III, randomized, multicenter, double-blind, placebo-controlled study (VALOR). In this study, the addition of vosaroxin produced a 1.4-month improvement in median overall survival (OS; 7.5 months with vosaroxin/cytarabine vs. 6.1 months with placebo/cytarabine; hazard ratio [HR] 0.87, 95 % confidence interval [CI] 0.73-1.02; unstratified log-rank p [Formula: see text] 0.061; stratified log-rank p [Formula: see text]0.024), with the greatest OS benefit observed in patients ≥60 years of age (7.1 vs. 5.0 months; HR 0.75, 95 % CI 0.62-0.92; p [Formula: see text]0.003) and patients with early relapse (6.7 vs. 5.2 months; HR 0.77, 95 % CI 0.59-1.00; p [Formula: see text] 0.039), two AML patient groups that typically have poor prognosis. Here we review the chemical and pharmacologic properties of vosaroxin, how these properties are distinct from those of currently available topoisomerase II inhibitors, how they may contribute to the efficacy and safety profile observed in the VALOR trial, and the status of clinical development of vosaroxin for treatment of AML. PMID:27484675

  3. Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

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    Vinayak Mahadev Adimule

    2014-12-01

    Full Text Available In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa, Caco-2 and MCF7. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole 4a-e. The 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e. Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

  4. Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis.

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    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Uzelac, Lidija; Jarak, Ivana; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kralj, Marijeta; Tomić, Sanja; Karminski-Zamola, Grace

    2012-06-14

    A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties.

  5. Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives

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    Nagatoshi Nishiwaki

    2010-07-01

    Full Text Available The 1-methyl-2-quinolone (MeQone framework is often found in alkaloids and recently attention was drawn to unnatural MeQone derivatives with the aim of finding new biologically active compounds, however, low reactivity of the MeQone framework prevents the syntheses of versatile derivatives. A nitro group is one of the useful activating groups for this framework that enables a concise chemical transformation. Among nitroquinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ exhibits unusual reactivity favoring region-selective cine-substitutions that afford 4-substituted 1-methyl-6,8-dinitro-2-quinolones upon treatment with nucleophilic reagents. Contrary to this, 1-methyl-3,6-dinitro-2-quinolone (3,6-DNQ does not undergo any reaction under the same conditions. The unusual reactivity of TNQ is caused by steric repulsion between the methyl group at the 1-position and the nitro group at the 8-position, which distorts the MeQone framework. As a result, the pyridone ring of TNQ loses aromaticity and acts rather as an activated nitroalkene. Indeed, the pyridone moiety of TNQ undergoes cycloaddition with electron-rich alkenes or dienes under mild conditions, whereby a new fused ring is constructed on the [c]-face of the MeQone. Consequently, TNQ can be used as a new scaffold leading to versatile unnatural MeQone derivatives.

  6. Design, synthesis and antitumor activity of 3-substituted quinolone derivatives (Ⅰ)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor cells are comparable to that of topotecan, one of topoisomerase I inhibitors.

  7. Isocorydine Derivatives and Their Anticancer Activities

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    Mei Zhong

    2014-08-01

    Full Text Available In order to improve the anticancer activity of isocorydine (ICD, ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino-isocorydine (8 and 6a,7-dihydrogen-isocorydione (10 could inhibit the growth of human lung (A549, gastric (SGC7901 and liver (HepG2 cancer cell lines in vitro. Isocorydione (2 could inhibit the tumor growth of murine sarcoma S180-bearing mice, and 8-acetamino-isocorydine (11, a pro-drug of 8-amino-isocorydine (8, which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent.

  8. Lanthanum triflate triggered synthesis of tetrahydroquinazolinone derivatives of N-allyl quinolone and their biological assessment

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    Jardosh Hardik H.

    2012-01-01

    Full Text Available A series of 24 derivatives of tetrahydroquinazolinone has been synthesized by one-pot cyclocondensation reaction of N-allyl quinolones, cyclic β-diketones and (thiourea/N-phenylthiourea in presence of lanthanum triflate catalyst. This methodology allowed us to achieve the products in excellent yield by stirring at room temperature. All the synthesized compounds were investigated against a representative panel of pathogenic strains using broth microdilution MIC (minimum inhibitory concentration method for their in vitro antimicrobial activity. Amongst these sets of heterocyclic compounds 5h, 6b, 6h, 5f, 5l, 5n and 6g found to have admirable activity.

  9. Synthesis and in vitro antibacterial activities of 7-(4-alkoxyimino-3-hydroxypiperidin-1-y1)quinolone derivatives

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of novel 7-(4-alkoxyimino-3-hydroxypiperidin-1-yl)quinolone derivatives were designed,synthesized and evaluated for in vitro antibacterial activities.Compounds 8f,8g,8i and 8j with the potencies similar to or better than those of levofloxacin and IMB against Staphylococcus aureus and Staphylococcus epidermidis,worth further investigation.

  10. Anilides and quinolones with nitrogen-bearing substituents from benzothiophene and thienothiophene series: synthesis, photochemical synthesis, cytostatic evaluation, 3D-derived QSAR analysis and DNA-binding properties.

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    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Depauw, Sabine; Martin-Kleiner, Irena; David-Cordonnier, Marie-Hélène; Tomić, Sanja; Kralj, Marijeta; Karminski-Zamola, Grace

    2014-01-01

    A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of photochemical dehydrohalogenation from corresponding anilides. Anilides and quinolones were tested for the antiproliferative activity. Fused quinolones bearing protonated aminium group, quaternary ammonium group, N-methylated and protonated aminium group, amino and protonated amino group (8a, 9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active one, having the IC50 concentration at submicromolar range in accordance with previous QSAR predictions. On the other hand, flexible anilides were among the less active. Chemometric analysis of investigated compounds was performed. 3D-derived QSAR analysis identified solubility, metabolitic stability and the possibility of the compound to be ionized at pH 4-8 as molecular properties that are positively correlated with anticancer activity of investigated compounds, while molecular flexibility, polarizability and sum of hydrophobic surface areas were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b, 8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases I/II inhibition as part of their mechanism of action. Among the anilides, only compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14, were clearly distinguished from the other compounds according to their molecular descriptors by the PCA and PLS analysis.

  11. Anticancer activities of artemisinin and its bioactive derivatives.

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    Firestone, Gary L; Sundar, Shyam N

    2009-01-01

    Artemisinin, a sesquiterpene lactone derived from the sweet wormwood plant Artemisia annua, and its bioactive derivatives exhibit potent anticancer effects in a variety of human cancer cell model systems. The pleiotropic response in cancer cells includes growth inhibition by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. These effects of artemisinin and its derivatives result from perturbations of many cellular signalling pathways. This review provides a comprehensive discussion of these cellular responses, and considers the ramifications for the potential development of artemisinin-based compounds in anticancer therapeutic and preventative strategies. PMID:19883518

  12. Novel derivatives of benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, and antitumor evaluation.

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    Dogan Koruznjak, Jasna; Grdisa, Mira; Slade, Neda; Zamola, Branimir; Pavelić, Kresimir; Karminski-Zamola, Grace

    2003-10-01

    Novel derivatives of benzo[b]thieno[2,3-c]quinolones 3a-j were synthesized in a multistep synthesis starting from substituted benzo[b]thiophene-2-carbonyl chlorides, to their corresponding benzo[b]thiophene-2-carboxamides, which were photochemically dehydrohalogenated to their corresponding substituted benzo[b]thieno[2,3-c]quinolones. Compound 4 was prepared from 3i by alkylation with 3-dimethylaminopropyl chloride in the presence of NaH. Compounds 7a,b were prepared from 3g in the multistep synthesis from compounds 5 and 6. Compounds 3b, 3c-f, 3h, 7a, and 7b were found to exert cytostatic activity against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), human fibroblast cell lines (WI-38). The compounds that bear a 3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma cells (HBL, ME 67.3, and ME 67.1), a potential mechanism of action was examined. Analysis of DNA and Annexin-V-FLUOS staining indicated that compound 4 causes cell death by apoptosis.

  13. Synthesis and anticancer evaluation of (-1)- aretigenin derivatives

    International Nuclear Information System (INIS)

    Seven (-)-arctigenin derivatives 1-7 were designed and synthesized by using Mannich and acylation methods to improve the activity and bioavailability of (-)-arctigenin. Structures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Anticancer activity of these compounds on SGC7901 was assayed in vitro. (author)

  14. Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives.

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    Manetti, Fabrizio; Petricci, Elena; Gabrielli, Annalisa; Mann, Andrè; Faure, Hélène; Gorojankina, Tatiana; Brasseur, Laurent; Hoch, Lucile; Ruat, Martial; Taddei, Maurizio

    2016-10-01

    Smoothened (Smo) is the signal transducer of the Hedgehog (Hh) pathway and its stimulation is considered a potential powerful tool in regenerative medicine to treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new quinolones (0.4-0.9 μM) is comparable to or better than that of SAG and purmorphamine, two reference Smo agonists. Structure-activity relationships allow identification of several molecular determinants important for the activity of these compounds. PMID:27429255

  15. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  16. Synthesis and Anticancer Activity of Novel Thiazole-5-Carboxamide Derivatives

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    Wen-Xi Cai

    2016-01-01

    Full Text Available A series of novel 2-phenyl-4-trifluoromethyl thiazole-5-carboxamide derivatives have been synthesized and evaluated for their anticancer activity against A-549, Bel7402, and HCT-8 cell lines. Among the tested compounds, highest activity (48% was achieved with the 4-chloro-2-methylphenyl amido substituted thiazole containing the 2-chlorophenyl group on the two position of the heterocyclic ring. Other structurally similar compounds displayed moderate activity. The key intermediates have been fully characterized.

  17. Synthesis and biological evaluation of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives as potential topoisomerase I inhibitors.

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    Ge, Raoling; Zhao, Qian; Xie, Zhouling; Lu, Lu; Guo, Qinglong; Li, Zhiyu; Zhao, Li

    2016-10-21

    The design and synthesis of a new series of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives, built on the structure of 1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone, are described. These compounds provide new scaffold for the discovery of Topoisomerase I (Top I) inhibitors and target based assay showed that they can obviously inhibited Top I at 100 μM. The in vitro anti-proliferative activity of these new compounds was evaluated against A549, Hela, BGC-823, and HepG2 cell lines. Compounds 18a-g showed potent inhibitory activity against the growth of those cancer cell lines. The most positive compounds 18f and 18g demonstrated as potent as camptothecin in Top I inhibition assay and MTT assay. Compounds 18f and 18g led to an obvious increase in the percentage of S phase of the cells in 24 h. The in vivo data showed that 18f and 18g inhibited tumor growth with the inhibitory rate of 29.25% and 42.75% at 20 mg/kg, respectively. The data suggested the therapeutic potential for further development. PMID:27416553

  18. New water soluble pyrroloquinoline derivatives as new potential anticancer agents.

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    Ferlin, Maria Grazia; Marzano, Christine; Dalla Via, Lisa; Chilin, Adriana; Zagotto, Giuseppe; Guiotto, Adriano; Moro, Stefano

    2005-08-01

    A new class of water soluble 3H-pyrrolo[3,2-f]quinoline derivatives has been synthesized and investigated as potential anticancer drugs. Water solubility profiles have been used to select the most promising derivatives. The novel compound 10, having two (2-diethylamino-ethyl) side chains linked through positions 3N and 9O, presents a suitable water solubility profile, and it was shown to exhibit cell growth inhibitory properties when tested against the in-house panel of cell lines, in particular those obtained from melanoma. PMID:15936202

  19. Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with 5-chloro-2-thienyl group

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    2008-08-01

    Full Text Available Background and the purpose of the study: Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Methods: Reaction of ciprofloxacin (1, norfloxacin (2 and enoxacin (3 with α-bromoketone 10 or α-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO3 at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7(a-c, respectively. Results and major conclusion: The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives (compounds 4a, 5a, 6a and 7a were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-(5-chlorothiophen-2-yl-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 μg/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug (ciprofloxacin against all Gram-positive bacteria with the exception of E. feacalis.

  20. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

    OpenAIRE

    Lesyk R. B.; Kaminskyy D. V.

    2010-01-01

    The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR) aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program). Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to...

  1. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

    OpenAIRE

    Gomes, Nelson G. M.; Florence Lefranc; Anake Kijjoa; Robert Kiss

    2015-01-01

    Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. ...

  2. Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Carboxamide Derivatives of 2-Quinolones

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    Abhishek Kumar

    2014-12-01

    Full Text Available A series of novel substituted N-(3-acetyl-2-oxoquinolin-1(2H-ylbenzamide (AJQC1-AJQC12 have been synthesized upon refluxing 3-acetyl-1-amino-quinolin-2-one and substituted benzoic acid in the presence of dry redistilled pyridine and silicon tetra chloride as coupling agent. 3-acetyl-1-amino-quinolin-2-one (AJQ1-AJQ12 were synthesized from substituted 3-acetyl coumarin upon refluxing with hydrazine hydrate and ethanol. The structures of the final carboxamide derivatives were confirmed by IR, 1H NMR and mass spectra. The synthesized compounds were screened for their antimicrobial activity by tube dilution method and anti tubercular activity by microplate Alamar blue assay. Most of the compounds have exhibited promising antibacterial, anti fungal and anti tubercular activities.

  3. Synthesis of Quinolone Analogues:7-[(2S, 4R)-2-Aminomethyl-4- hydroxypyrrolidin-1-yl] Quinolones

    Institute of Scientific and Technical Information of China (English)

    Jiu Yu LIU; Hui Yuan GUO

    2004-01-01

    New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone-3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.

  4. Synthesis, Spectroscopic and Antimicrobial Studies of Transition Metal Complexes of N-Amino Quinolone Derivatives

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    R.I.H. AL-Bayati

    2011-02-01

    Full Text Available In Iraq like most third world countries, attempts to discovered a new antibiotic drugs derived from coumarin and its metal complexes moreover develop the branch of applied in organic chemistry. Novel transition metal(II complexes, [M(L12Cl2] and [M(L22Cl2], were synthesized from the reaction of MCl2.nH2O (M = Co, Ni, Cu with (Z-1-(1-(1H-indol-3-ylethylideneaminoquinolin-2(1H-one (L1 or (E-1-(2- hydroxybenzylideneaminoquinolin-2(1H-one (L2. The ligands were obtained from coumarin. N-amino quinoline-2-one (2 has been synthesized by the reflux of coumarin (1 with hydrazine hydrate in ethanol for 12 h. The azomethines (L1, L2 were prepared from the corresponding aryl carbonyls. The synthesized compounds were and characterized by element chemical analysis, molar conductance, magnetic susceptibility measurements, and spectral (electronic, and FT-IR studies. The IR spectral data suggest the involvement of sulphur and azomethane nitrogen in coordination to the central metal ion. On the basis of spectral studies, an octahedral geometry has been assigned for all complexes. The free ligands and its metal complexes have been tested in vitro against a number of microorganisms in order to assess their antimicrobial properties.

  5. Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 8-chloro-4-hydroxyl-2-quinolone

    Science.gov (United States)

    Yahyazadeh, Asieh; Yousefi, Hessamoddin

    2014-01-01

    In this study, 8-chloro-4-hydroxyl-2-quinolone was synthesized from cyclocondensation of corresponding dianilide and subsequently used as a potent coupling component with some diazotized heterocyclic amines. These compounds were characterized by UV-vis, FT-IR, 1H NMR spectroscopic techniques and elemental analysis. Absorption spectra of these dyes were measured in six polar solvents and discussed with respect to the nature of solvents and substituted groups. The effects of acid, base, temperature and concentration on the visible absorption spectra of the dyes were reported. In addition, the antimicrobial activity of the dyes was explored in detail.

  6. Design and synthesis of novel soluble 2,5-diketopiperazine derivatives as potential anticancer agents.

    Science.gov (United States)

    Liao, Shengrong; Qin, Xiaochu; Li, Ding; Tu, Zhengchao; Li, Jinsheng; Zhou, Xuefeng; Wang, Junfeng; Yang, Bin; Lin, Xiuping; Liu, Juan; Yang, Xianwen; Liu, Yonghong

    2014-08-18

    Non-protected 2,5-diketopiperazine derivatives have poor solubility thus with negative impact on their bioavailability. In the present study, twenty-one novel soluble mono-protected, and three non-protected 2,5-diketopiperazine derivatives were designed and synthesized. Their anticancer activity to ten cell lines were evaluated by using CCK8 assay, and the results showed that about half of the mono-protected derivatives had broad-spectrum anticancer activity. Among allyl-protected derivatives, compound 4m had strong activity to all the cell lines (IC50 = 0.5-4.5 μM), especially to the cancer cell lines U937 (IC50 = 0.5 μM) and K562 (IC50 = 0.9 μM). Compound 4m could become a lead compound for further development for anticancer agents.

  7. Structure–anticancer activity relationships among 4-azolidinone-3-carboxylic acids derivatives

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    Lesyk R. B.

    2010-04-01

    Full Text Available The aim of present research was investigation of anticancer activity of 4-azolidinone-3-carboxylic acids derivatives, and studies of structure–activity relationships (SAR aspects. Methods. Organic synthesis; spectral methods; anticancer screening was performed according to the US NCI protocol (Developmental Therapeutic Program. Results. The data of new 4-thiazolidinone-3-alkanecarboxylic acids derivatives in vitro anticancer activity were described. The most active compounds which belong to 5-arylidene-2,4- thia(imidazolidinone-3-alkanecarboxylic acids; 5-aryl(heterylidenerhodanine-3-succinic acids derivatives were selected. Determination of some SAR aspects which allowed to determine directions in lead- compounds structure optimization, as well as desirable molecular fragments for design of potential anticancer agents based on 4-azolidinone scaffold were performed. 5-Arylidenehydantoin-3-acetic acids amides were identified as a new class of significant selective antileukemic agents. Possible pharmacophore scaffold of 5-ylidenerhodanine-3-succinic acids derivatives was suggested. Conclusions. The series of active compounds with high anticancer activity and/or selectivity levels were selected. Some SAR aspects were determined and structure design directions were proposed.

  8. Recent developments of C-4 substituted coumarin derivatives as anticancer agents.

    Science.gov (United States)

    Dandriyal, Jyoti; Singla, Ramit; Kumar, Manvendra; Jaitak, Vikas

    2016-08-25

    Cancer is a prominent cause of death in global. Currently, the numbers of drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Researchers have made an attempt to expand a suitable anticancer drug that has no MDR and side effect. Coumarin scaffold became an attractive subject due to their broad spectrum of pharmacological activities. Coumarin derivatives extensively explored for anticancer activities as it possesses minimum side effect along with multi-drug reversal activity. Coumarin derivatives can act by various mechanisms on different tumor cell lines depending on substitution pattern of the core structure of coumarin. Substitution on coumarin nucleus leads to the search for more potent compounds. In this review, we have made an effort to give a synthetic strategy for the preparation of C-4 substituted coumarin derivatives as anticancer agents based on their mechanism of action and also discuss the SAR of the most active compound.

  9. Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

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    Luana da S. M. Forezi

    2014-05-01

    Full Text Available As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells.

  10. Metal Complexes of Quinolone Antibiotics and Their Applications: An Update

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    Valentina Uivarosi

    2013-09-01

    Full Text Available Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle at the 7-position, and a carbonyl oxygen atom at the 4-position quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  11. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis.

    Science.gov (United States)

    Gali-Muhtasib, Hala; Hmadi, Raed; Kareh, Mike; Tohme, Rita; Darwiche, Nadine

    2015-12-01

    Despite remarkable progress in the discovery and development of novel cancer therapeutics, cancer remains the second leading cause of death in the world. For many years, compounds derived from plants have been at the forefront as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability, and relatively low toxicity when compared with chemotherapy. More than 3000 plant species have been reported to treat cancer and about thirty plant-derived compounds have been isolated so far and have been tested in cancer clinical trials. The mechanisms of action of plant-derived anticancer drugs are numerous and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and caspase and/or p53-dependent or independent mechanisms. Alternative modes of cell death by plant-derived anticancer drugs are emerging and include mainly autophagy, necrosis-like programmed cell death, mitotic catastrophe, and senescence leading to cell death. Considering that the non-apoptotic cell death mechanisms of plant-derived anticancer drugs are less reviewed than the apoptotic ones, this paper attempts to focus on such alternative cell death pathways for some representative anticancer plant natural compounds in clinical development. In particular, emphasis will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids such as parthenolide, triptolide, and betulinic acid; and the organosulfur compound sulforaphane. The understanding of non-apoptotic cell death mechanisms induced by these drugs would provide insights into the possibility of exploiting novel molecular pathways and targets of plant-derived compounds for future cancer therapeutics. PMID:26362468

  12. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

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    Gomes, Nelson G M; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

    2015-06-01

    Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms. PMID:26090846

  13. Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

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    Nelson G. M. Gomes

    2015-06-01

    Full Text Available Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i selectivity between normal and cancer cells (ii activity against multidrug-resistant (MDR cancer cells; and (iii a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

  14. Plant derived substances with anti-cancer activity: from folklore to practice

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    Marcelo eFridlender

    2015-10-01

    Full Text Available Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.

  15. Plant derived substances with anti-cancer activity: from folklore to practice.

    Science.gov (United States)

    Fridlender, Marcelo; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century. This trend led to the discovery of different active compounds that are derived from plants. In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity. Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next two decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities. Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin, and cannabinoids. In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity. PMID:26483815

  16. Design, synthesis and biological activity of piperlongumine derivatives as selective anticancer agents.

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    Wu, Yuelin; Min, Xiao; Zhuang, Chunlin; Li, Jin; Yu, Zhiliang; Dong, Guoqiang; Yao, Jiangzhong; Wang, Shengzheng; Liu, Yang; Wu, Shanchao; Zhu, Shiping; Sheng, Chunquan; Wei, Yunyang; Zhang, Huojun; Zhang, Wannian; Miao, Zhenyuan

    2014-07-23

    In an effort to expand the structure-activity relationship of the natural anticancer compound piperlongumine, we have prepared sixteen novel piperlongumine derivatives with halogen or morpholine substituents at C2 and alkyl substituents at C7. Most of 2-halogenated piperlongumines showed potent in vitro activity against four cancer cells and modest selectivity for lung normal cells. The highly active anticancer compound 11h exhibited obvious ROS elevation and excellent in vivo antitumor potency with suppressed tumor growth by 48.58% at the dose of 2 mg/kg. The results indicated that halogen substituents as electrophilic group at C2 played an important role in increasing cytotoxicity. PMID:24937186

  17. Design, synthesis, and mechanistic studies of Sansalvamide A derivatives as anti-cancer agents

    OpenAIRE

    Alexander, Leslie Diane

    2012-01-01

    Sansalvamide A (SanA) is a cyclic depsipeptide that was isolated from a marine fungus and demonstrates mid- micromolar anti-cancer activity in the NCI 60-cell line panel. Our laboratory has synthesized over 100 peptide derivatives of this molecule, 5 of which were contributed by the author of this dissertation. The design and solution-phase synthesis of these derivatives is described in Chapter 2. The author was also responsible for attaching PEG-biotin and fluorescein tags to lead SanA deriv...

  18. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    Science.gov (United States)

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  19. New 1,4-anthracene-9,10-dione derivatives as potential anticancer agents.

    Science.gov (United States)

    Zagotto, G; Supino, R; Favini, E; Moro, S; Palumbo, M

    2000-01-01

    The amino-substituted anthracene-9,10-dione (9,10-anthraquinone) derivatives represent one of the most important classes of potential anticancer agents. To better understand the basic rules governing DNA sequence specificity, we have recently synthesized a new class of D- and L-aminoacyl-anthraquinone derivatives. We have tested these new compounds as cytotoxic agents, and we have correlated their activity with the configuration of the chiral aminoacyl moiety. Molecular modeling studies have been performed to compare the test drugs in terms of steric overlapping. PMID:10755224

  20. Synthesis, characterization and anticancer studies of new steroidal oxadiazole, pyrrole and pyrazole derivatives

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    Shamsuzzaman

    2015-07-01

    Full Text Available In the present study steroidal derivatives, 3β-[5′-mercapto-1′,3′,4′-oxadiazole-2-yl]methoxy cholest-5-ene 2, 3β-[2′,5′-dimethylpyrrole-1-yl]aminocarbonylmethoxycholest-5-ene 3 and 3β-[3′,5′-dimethyl pyrazole-1-yl]carbonylmethoxycholest-5-ene 4 have been synthesized from cholest-5-en-3β-O-acetyl hydrazide 1 using CS2/KOH, acetonyl acetone and acetyl acetone, respectively as reagents and are characterized by IR, 1H NMR,13C NMR, MS and elemental analysis. Compounds 2–4 were also evaluated for anticancer activity against human leukemia cell line (HL-60 by MTT assay and compound 4 displayed the promising behavior by showing better anticancer activity.

  1. Adding pharmacogenomics to the development of new marine-derived anticancer agents

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    Aracil Miguel

    2006-01-01

    Full Text Available Abstract Nature has always been a highly productive tool in the development of anticancer therapies. Renewed interest in the potential of this tool has recently been sparked by the realization that the marine ecosystem can be used for the discovery and development of new compounds with clinical potential in advanced resistant tumors. These compounds can be incorporated into combination approaches in a chronic therapy scenario. Our marine anticancer program is using the sea to develop new agents with activity in resistant solid tumors and to identify new cellular targets for therapeutic intervention. This review describes the integration of different pharmacogenomic tools in the development of Yondelis™, Aplidin® and Kahalalide F, three marine-derived compounds currently in Phase II or III development. Our results are reinforcing the targeted selectivity of these agents and opening the gates for customized therapies in cancer patients in the near future.

  2. Anticancer Activity of Some New Synthesized Tetrahydroquinoline and Tetrahydrochromene Carbonitrile Derivatives

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    Usama W. Hawas

    2011-01-01

    Full Text Available Problem statement: In continuation to our search for new heterocyclic chemistry based anticancer, the suggestion, synthesis, structure elucidation of some naphthalene, chromene and quinoline derivatives 3-7 were realized herein using 3-methylcyclohexanone 1 as a starting material. Approach: The antitumor activities of the newly synthesized compounds 4-7 were evaluated utilizing 60 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast and prostate as well as kidney. Results: Some of the tested compounds exhibited better in vitro antitumor activities at low concentration (log10 GI50 = -4.7 against the used human tumor cell lines. Conclusion: From the obtained results, we can conclude that cyanopyridine and pyrane moieties fused to 3-methycyclohexane ring are essential for antitumor activities. In the present work, we can suggest that the anticancer activity is due to the presence of nitrogen heterocyclic rings and the presence of the nitrile groups (CN generally enhancing the activity.

  3. Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents.

    Science.gov (United States)

    Zhu, Xiong; Fu, Junjie; Tang, Yan; Gao, Yuan; Zhang, Shijin; Guo, Qinglong

    2016-02-15

    A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent. PMID:26804229

  4. Amino acid esters substituted phosphorylated emtricitabine and didanosine derivatives as antiviral and anticancer agents.

    Science.gov (United States)

    Sekhar, Kuruva Chandra; Janardhan, Avilala; Kumar, Yellapu Nanda; Narasimha, Golla; Raju, Chamarthi Naga; Ghosh, S K

    2014-07-01

    Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition. PMID:24789416

  5. QSAR and docking studies on xanthone derivatives for anticancer activity targeting DNA topoisomerase IIα

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    Alam S

    2014-01-01

    Full Text Available Sarfaraz Alam, Feroz KhanMetabolic and Structural Biology Department, Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, IndiaAbstract: Due to the high mortality rate in India, the identification of novel molecules is important in the development of novel and potent anticancer drugs. Xanthones are natural constituents of plants in the families Bonnetiaceae and Clusiaceae, and comprise oxygenated heterocycles with a variety of biological activities along with an anticancer effect. To explore the anticancer compounds from xanthone derivatives, a quantitative structure activity relationship (QSAR model was developed by the multiple linear regression method. The structure–activity relationship represented by the QSAR model yielded a high activity–descriptors relationship accuracy (84% referred by regression coefficient (r2=0.84 and a high activity prediction accuracy (82%. Five molecular descriptors – dielectric energy, group count (hydroxyl, LogP (the logarithm of the partition coefficient between n-octanol and water, shape index basic (order 3, and the solvent-accessible surface area – were significantly correlated with anticancer activity. Using this QSAR model, a set of virtually designed xanthone derivatives was screened out. A molecular docking study was also carried out to predict the molecular interaction between proposed compounds and deoxyribonucleic acid (DNA topoisomerase IIα. The pharmacokinetics parameters, such as absorption, distribution, metabolism, excretion, and toxicity, were also calculated, and later an appraisal of synthetic accessibility of organic compounds was carried out. The strategy used in this study may provide understanding in designing novel DNA topoisomerase IIα inhibitors, as well as for other cancer targets.Keywords: drug likeness, ADMET, regression model, HeLa cell line

  6. Anthracenedione Derivatives as Anticancer Agents Isolated from Secondary Metabolites of the Mangrove Endophytic Fungi

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    Jian-ye Zhang

    2010-04-01

    Full Text Available In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403 and Guignardia sp. (No. 4382. Some of them inhibited potently the growth of KB and KBv200 cells, among which compound 6 displayed strong cytotoxicity with IC50 values of 3.17 and 3.21 μM to KB and KBv200 cells, respectively. Furthermore, we demonstrate that the mechanism involved in the apoptosis induced by compound 6 is probably related to mitochondrial dysfunction. Additionally, the structure-activity relationships of these compounds are discussed.

  7. Synthesis, crystal structure, superoxide scavenging activity, anticancer and docking studies of novel adamantyl nitroxide derivatives

    Science.gov (United States)

    Zhu, Xiao-he; Sun, Jin; Wang, Shan; Bu, Wei; Yao, Min-na; Gao, Kai; Song, Ying; Zhao, Jin-yi; Lu, Cheng-tao; Zhang, En-hu; Yang, Zhi-fu; Wen, Ai-dong

    2016-03-01

    A novel adamantyl nitroxide derivatives has been synthesized and characterized by IR, ESI-MS and elemental analysis. Quantum chemical calculations have also been performed to calculate the molecular geometry using density functional theory (B3LYP) with the 6-31G (d,p) basis set. The calculated results showed that the optimized geometry can well reproduce the crystal structure. The antioxidant and antiproliferative activity were evaluated by superoxide (NBT) and MTT assay. The adamantyl nitroxide derivatives exhibited stronger scavenging ability towards O2· - radicals when compared to Vitamin C, and demonstrated a remarked anticancer activity against all the tested cell lines, especially Bel-7404 cells with IC50 of 43.3 μM, compared to the positive control Sorafenib (IC50 = 92.0 μM). The results of molecular docking within EGFR using AutoDock confirmed that the titled compound favorably fitted into the ATP binding site of EGFR and would be a potential anticancer agent.

  8. Apigenin as an anti-quinolone-resistance antibiotic.

    Science.gov (United States)

    Morimoto, Yuh; Baba, Tadashi; Sasaki, Takashi; Hiramatsu, Keiichi

    2015-12-01

    We previously reported the first 'reverse antibiotic' (RA), nybomycin (NYB), which showed a unique antimicrobial activity against Staphylococcus aureus strains. NYB specifically suppressed the growth of quinolone-resistant S. aureus strains but was not effective against quinolone-susceptible strains. Although NYB was first reported in 1955, little was known about its unique antimicrobial activity because it was before the synthesis of the first quinolone ('old quinolone'), nalidixic acid, in 1962. Following our re-discovery of NYB, we looked for other RAs among natural substances that act on quinolone-resistant bacteria. Commercially available flavones were screened against S. aureus, including quinolone-resistant strains, and their minimum inhibitory concentrations (MICs) were compared using the microbroth dilution method. Some of the flavones screened showed stronger antimicrobial activity against quinolone-resistant strains than against quinolone-susceptible ones. Amongst them, apigenin (API) was the most potent in its RA activity. DNA cleavage assay showed that API inhibited DNA gyrase harbouring the quinolone resistance mutation gyrA(Ser84Leu) but did not inhibit 'wild-type' DNA gyrase that is sensitive to levofloxacin. An API-susceptible S. aureus strain Mu50 was also selected using agar plates containing 20mg/L API. Whole-genome sequencing of selected mutant strains was performed and frequent back-mutations (reverse mutations) were found among API-resistant strains derived from the API-susceptible S. aureus strains. Here we report that API represents another molecular class of natural antibiotic having RA activity against quinolone-resistant bacteria. PMID:26526895

  9. A QSAR study and molecular design of benzothiazole derivatives as potent anticancer agents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by "leave-one-out" (LOO) cross-validation coefficient (q2n-i) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MRR) and the net charge (QFR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (lgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R2) and the cross-validation coefficient (q2) values are 0.883 and 0.797, respectively. It indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

  10. Novel cyano- and N-isopropylamidino-substituted derivatives of benzo[b]thiophene-2-carboxanilides and benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, crystal structure determination, and antitumor evaluation. 2.

    Science.gov (United States)

    Jarak, Ivana; Kralj, Marijeta; Suman, Lidija; Pavlović, Gordana; Dogan, Jasna; Piantanida, Ivo; Zinić, Mladen; Pavelić, Kresimir; Karminski-Zamola, Grace

    2005-04-01

    Derivatives of 3-chlorobenzo[b]thiophene-2-carboxanilides and their "cyclic" analogues benzo[b]thieno[2,3-c]quinolones were synthesized. Spectroscopic study of the interactions of some representatives of "cyclic" derivatives and their "acyclic" precursors with ds-DNA/RNA supported strong intercalative binding of the former and weak nonintercalative binding of the latter group of compounds. All tested compounds showed a certain antiproliferative effect on a series of human tumor cells and on a normal cell line. Among the compounds, those with one amidino-substituent have shown the best effect. The most active benzo[b]thieno[2,3-c]quinolones induced apparent S and G2/M arrests of the cell cycle, which resulted in apoptosis. These results strongly suggest that the compounds may act as topoisimerase "poisons", which is in good agreement with their intercalative mode of binding to ds-DNA/RNA, in contrast to the studied "acyclic"group of derivatives. 6a and 6d showed the best selectivity by inhibiting the growth of tumor cells but not of normal fibroblasts.

  11. Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents.

    Science.gov (United States)

    Altıntop, Mehlika Dilek; Atlı, Özlem; Ilgın, Sinem; Demirel, Rasime; Özdemir, Ahmet; Kaplancıklı, Zafer Asım

    2016-01-27

    New thiosemicarbazone derivatives (1-10) were obtained via the reaction of 4-(naphthalen-1-yl)thiosemicarbazide with fluoro-substituted aromatic aldehydes. The synthesized compounds were evaluated for their in vitro antifungal effects against pathogenic yeasts and molds using broth microdilution assay. Ames and umuC assays were carried out to determine the genotoxicity of the most effective antifungal derivatives. Furthermore, all compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using XTT test. Among these derivatives, 4-(naphthalen-1-yl)-1-(2,3-difluorobenzylidene)thiosemicarbazide (1) and 4-(naphthalen-1-yl)-1-(2,5-difluorobenzylidene)thiosemicarbazide (3) can be identified as the most promising antifungal derivatives due to their notable inhibitory effects on Candida species and no cytotoxicity against NIH/3T3 mouse embryonic fibroblast cell line. According to Ames and umuC assays, compounds 1 and 3 were classified as non-mutagenic compounds. On the other hand, 4-(naphthalen-1-yl)-1-(2,4-difluorobenzylidene)thiosemicarbazide (2) can be considered as the most promising anticancer agent against A549 cell line owing to its notable inhibitory effect on A549 cells with an IC50 value of 31.25 μg/mL when compared with cisplatin (IC50 = 16.28 μg/mL) and no cytotoxicity against NIH/3T3 cells. PMID:26706351

  12. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent.

    Science.gov (United States)

    Noolvi, Malleshappa N; Patel, Harun M; Bhardwaj, Varun; Chauhan, Ankit

    2011-06-01

    The synthesis of some 2-furano-4(3H)-quinazolinones, diamides (open ring quinazolines), quinoxalines and their biological evaluation as antitumor agents using National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Among the synthesize compounds, seventeen compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the selected compounds, 3-(2-chloro benzylideneamine)-2-(furan-2-yl) quinazoline-4(3h)-one 21 was found to be the most active candidate of the series at five dose level screening against Ovarian OVCAR-4 and Non-small cell lung cancer NCI-H522 with GI50 1.82 & 2.14 μM respectively. Rational approach and QSAR techniques enabled the understanding of the pharmacophoric requirement for quinazoline, diamides and quinoxaline derivatives.

  13. N-Phenyl-2-p-tolylthiazole-4-carboxamide derivatives: Syn-thesis and cytotoxicity evaluation as anticancer agents

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    Ahmad Mohammadi-Farani

    2014-07-01

    Conclusion: A new series of phenylthiazole derivatives were synthesized and their anticancer activity was assessed against cancerous cell lines. More structural modifications and derivatization is necessary to achieve to the more potent compounds.       

  14. Progress Toward the Development of Noscapine and Derivatives as Anticancer Agents.

    Science.gov (United States)

    DeBono, Aaron; Capuano, Ben; Scammells, Peter J

    2015-08-13

    Many nitrogen-moiety containing alkaloids derived from plant origins are bioactive and play a significant role in human health and emerging medicine. Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, has been used as a cough suppressant since the mid 1950s, illustrating a good safety profile. Noscapine has since been discovered to arrest cells at mitosis, albeit with moderately weak activity. Immunofluorescence staining of microtubules after 24 h of noscapine exposure at 20 μM elucidated chromosomal abnormalities and the inability of chromosomes to complete congression to the equatorial plane for proper mitotic separation ( Proc. Natl. Acad. Sci. U. S. A. 1998 , 95 , 1601 - 1606 ). A number of noscapine analogues possessing various modifications have been described within the literature and have shown significantly improved antiprolific profiles for a large variety of cancer cell lines. Several semisynthetic antimitotic alkaloids are emerging as possible candidates as novel anticancer therapies. This perspective discusses the advancing understanding of noscapine and related analogues in the fight against malignant disease. PMID:25811651

  15. Photoprocesses in quinolone substituted

    Science.gov (United States)

    Vasilyeva, N. Y.; Vusovich, O. V.

    2002-03-01

    In the present work the analysis of the possible ways of energy degradation of electron excited states of 4-methyl-7- hydxyquinolone-2 (Q) and its protolytic species is presented (Figure 1); a ratio of radiative and nonradiative channels of deactivation of energy of electronic excitation is established; constants of photophysical processes (internal and intercrossing conversion), proceeding after act of absorption of light are designed. Study of exited state intramolecular proton transfer (ESIPT) in quinolones is interesting as a source of information on the relative importance of these processes in the photophysics and photochemistry of such molecular systems.

  16. A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2012

    Directory of Open Access Journals (Sweden)

    Wamtinga Richard Sawadogo

    2015-04-01

    Full Text Available Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs.

  17. A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2011

    Directory of Open Access Journals (Sweden)

    Marc Diederich

    2013-03-01

    Full Text Available Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study of structure-function relationships has allowed synthesis of analogues with increased efficacy and less toxicity. In this report, we aim to review 42 compounds of marine origin and their derivatives that were published in 2011 as promising anticancer compounds.

  18. Design, Synthesis and Biological Evaluation of Novel Bromophenol Derivatives Incorporating Indolin-2-One Moiety as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Li-Jun Wang

    2015-02-01

    Full Text Available A series of bromophenol derivatives containing indolin-2-one moiety were designed and evaluated that for their anticancer activities against A549, Bel7402, HepG2, HeLa and HCT116 cancer cell lines using MTT assay in vitro. Among them, seven compounds (4g–4i, 5h, 6d, 7a, 7b showed potent activity against the tested five human cancer cell lines. Wound-healing assay demonstrated that compound 4g can be used as a potent compound for inactivating invasion and metastasis by inhibiting the migration of cancer cells. The structure–activity relationships (SARs of bromophenol derivatives had been discussed, which were useful for exploring and developing bromophenol derivatives as novel anticancer drugs.

  19. Recent Development of Copolymeric Delivery System for Anticancer Agents Based on Cyclodextrin Derivatives.

    Science.gov (United States)

    Feng, Runliang; Deng, Peizong; Teng, Fangfang; Song, Zhimei

    2016-01-01

    Core-shell structured aggregates of amphiphilic block copolymer are hopefully drug delivery system because of their ability to encapsulate hydrophobic drugs, and their hydrophilic shell can prolong retention time of drugs in the blood circulation system. Cyclodextrin is a kind of hydrophilic polysaccharide containing multiple hydroxyl groups, providing an inner hole that can load small molecule through host-guest interaction. These hydroxyl groups or their derived functional ones are utilized in conjugation with polymeric chains to form block copolymers. These copolymers can not only encapsulate hydrophobic drugs, but also encapsulate hydrophilic drugs (like DNA, protein, etc) through hydrophobic, host-guest or electrostatic interactions, which strengthen interaction between drugs and materials compared with general copolymers, indicating that formed drug delivery systems are more stable. By introduction of target molecule, they also achieve selective delivery of drugs to specific tissues or organs. So, several researchers are stimulated to carry out many studies for the development of cyclodextrin copolymeric drug delivery systems in recent. In this review, we focus the cyclodextrin copolymers' application in the anticancer agents' delivery. PMID:26349814

  20. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety.

    Science.gov (United States)

    Bingul, Murat; Tan, Owen; Gardner, Christopher R; Sutton, Selina K; Arndt, Greg M; Marshall, Glenn M; Cheung, Belamy B; Kumar, Naresh; Black, David StC

    2016-01-01

    Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G₁ cell cycle arrest, as well as upregulation of the p27(kip1) cell cycle regulating protein. PMID:27428941

  1. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

    Directory of Open Access Journals (Sweden)

    Murat Bingul

    2016-07-01

    Full Text Available Identification of the novel (E-N′-((2-chloro-7-methoxyquinolin-3-ylmethylene-3-(phenylthiopropanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27kip1 cell cycle regulating protein.

  2. Spectroscopic and structural studies of quinoline derivatives—II. Forrier transform i.r. spectroscopy. 1. Rotational isomerism in 3-ethoxycarbonyl-4(1H)-quinolone and some of its substituted derivatives,

    Science.gov (United States)

    Mirek, Julian; Urbanek, Zbigniew H.

    Rotational isomerism associated with internal rotation about the ring carbon(3)-ester carbonyl carbon single bond in a series of 3-ethoxycarbonyl-4(1H)-quinolones have been investigated spectroscopically in the solid state using Fourier transform i.r. and laser Raman spectroscopy. Particular attention is given to the 1700, 1300 and 1100 cm -1 spectral regions related primarily to the vibrations of the CO 2C 2H 5 group. Within these regions rotational isomerism appeared in the compounds examined. The conformational changes are discussed and evidence is reported for occurrence of the unsubstituted compound 1 itself in the solid state at ambient temperature as an equilibrium mixture of both the s-trans ( 1a) and s-cis ( 1b) rotamers (this is in contrast to previous findings), and of its Bz-substituted derivatives.

  3. Towards targeting anticancer drugs: ruthenium(ii)-arene complexes with biologically active naphthoquinone-derived ligand systems.

    Science.gov (United States)

    Kubanik, Mario; Kandioller, Wolfgang; Kim, Kunwoo; Anderson, Robert F; Klapproth, Erik; Jakupec, Michael A; Roller, Alexander; Söhnel, Tilo; Keppler, Bernhard K; Hartinger, Christian G

    2016-08-16

    Anticancer active metal complexes with biologically active ligands have the potential to interact with more than one biological target, which could help to overcome acquired and/or intrinsic resistance of tumors to small molecule drugs. In this paper we present the preparation of 2-hydroxy-[1,4]-naphthoquinone-derived ligands and their coordination to a Ru(II)(η(6)-p-cymene)Cl moiety. The synthesis of oxime derivatives resulted in the surprising formation of nitroso-naphthalene complexes, as confirmed by X-ray diffraction analysis. The compounds were shown to be stable in aqueous solution but reacted with glutathione and ascorbic acid rather than undergoing reduction. One-electron reduction with pulse radiolysis revealed different behavior for the naphthoquinone and nitroso-naphthalene complexes, which was also observed in in vitro anticancer assays. PMID:27214822

  4. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC “click” chemistry as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Jin X

    2014-08-01

    Full Text Available Xin Jin1,2,* Tian-Hua Yan,3,* Lan Yan,1 Qian Li,4 Rui-Lian Wang,1 Zhen-Lin Hu,1 Yuan-Ying Jiang,1 Qing-Yan Sun,1 Yong-Bing Cao1 1School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2School of Pharmacy, FuJian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China; 3Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China; 4Diakite Biological Technology Co., Ltd, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast, SW-1990 (pancreatic, and SMMC-7721 (liver and the noncancerous human umbilical vein endothelial cell (HUVEC cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50 values of 8.54±1.97 µM and 11.87±1.83 µM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 µM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 µM and 30.47±3.47 µM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC. Keywords: berberine, anticancer, click chemistry, structure–activity relationship

  5. Adding pharmacogenomics to the development of new marine-derived anticancer agents

    OpenAIRE

    Aracil Miguel; Jimeno José; Tercero Juan

    2006-01-01

    Abstract Nature has always been a highly productive tool in the development of anticancer therapies. Renewed interest in the potential of this tool has recently been sparked by the realization that the marine ecosystem can be used for the discovery and development of new compounds with clinical potential in advanced resistant tumors. These compounds can be incorporated into combination approaches in a chronic therapy scenario. Our marine anticancer program is using the sea to develop new agen...

  6. Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells.

    Science.gov (United States)

    Altintop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Kuş, Gökhan; Oztopcu-Vatan, Pinar; Kabadere, Selda; Kaplancikli, Zafer Asim

    2016-06-01

    Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect. PMID:25826149

  7. Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Grima, M.; Beguin, M.F.; Millanvoye-Van Brussel, E.M.; Decker, N.; Schwartz, J.

    1988-09-01

    To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on /sup 22/Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance /sup 22/Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the /sup 22/Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs.

  8. Induction of caspase 8 and reactive oxygen species by ruthenium-derived anticancer compounds with improved water solubility and cytotoxicity.

    Science.gov (United States)

    Vidimar, Vania; Meng, Xiangjun; Klajner, Marcelina; Licona, Cynthia; Fetzer, Ludivine; Harlepp, Sébastien; Hébraud, Pascal; Sidhoum, Marjorie; Sirlin, Claude; Loeffler, Jean-Philippe; Mellitzer, Georg; Sava, Gianni; Pfeffer, Michel; Gaiddon, Christian

    2012-12-01

    Organometallic compounds which contain metals, such as ruthenium or gold, have been investigated as a replacement for platinum-derived anticancer drugs. They often show good antitumor effects, but the identification of their precise mode of action or their pharmacological optimization is still challenging. We have previously described a class of ruthenium(II) compounds with interesting anticancer properties. In comparison to cisplatin, these molecules have lower side effects, a reduced ability to interact with DNA, and they induce cell death in absence of p53 through CHOP/DDIT3. We have now optimized these molecules by improving their cytotoxicity and their water solubility. In this article, we demonstrate that by changing the ligands around the ruthenium we modify the ability of the compounds to interact with DNA. We show that these optimized molecules reduce tumor growth in different mouse models and retain their ability to induce CHOP/DDIT3. However, they are more potent inducers of cancer cell death and trigger the production of reactive oxygen species and the activation of caspase 8. More importantly, we show that blocking reactive oxygen species production or caspase 8 activity reduces significantly the activity of the compounds. Altogether our data suggest that water-soluble ruthenium(II)-derived compounds represent an interesting class of molecules that, depending on their structures, can target several pro-apoptotic signaling pathways leading to reactive oxygen species production and caspase 8 activation. PMID:22964219

  9. The Pseudomonas Quinolone Signal (PQS)

    DEFF Research Database (Denmark)

    Sams, Thomas; Baker, Ysobel; Hodgkinson, James;

    2015-01-01

    is now known to be under the con-trol of the quorum sensing (QS) system. Over the last15 years, the Pseudomonas quinolone signal (PQS) has beenfound to play a crucial role in QS by linking the two seg-ments (las and rhl) of the P. aeruginosa N-acylhomoserinelactone-dependent QS signaling pathways...

  10. Molecular modeling studies and synthesis of novel quinoxaline derivatives with potential anticancer activity as inhibitors of c-Met kinase.

    Science.gov (United States)

    Abbas, Hebat-Allah S; Al-Marhabi, Aisha R; Eissa, Sally I; Ammar, Yousry A

    2015-10-15

    In an effort to develop potent anti-cancer agents, we have synthesized some substituted quinoxaline derivatives. Reaction of 6-bromo-3-methylquinoxalin-2(1H)-one 1 with aromatic aldehydes furnished the styryl derivatives 2a-e. Alkylation of 1 with ethyl chloroacetate produced the N-alkyl derivatives 3. Hydrazinolysis of the ester derivative 3 with hydrazine hydrate afforded the hydrazide derivative 4. In addition, chlorination of 1 with phosphorus oxychloride afforded the 2-chloro derivative 5 which was used as a key intermediate for the synthesis of substituted quinoxaline derivatives 6-8, N-pyrazole derivative 9, tetrazolo[1,5-a]quinoxaline derivative 10 and Schiff base derivatives 13, 15 via reaction with several nucleophiles reagents. Docking methodologies were used to predict their binding conformation to explain the differences of their tested biological activities. All the tested compounds were screened in vitro for their cytotoxic effect on three tumor cell lines. Some new quinoxaline derivatives were studied as inhibitors of c-Met kinase, a receptor associated with high tumor grade and poor prognosis in a number of human cancers. Compounds 2e, 4, 7a, 12a, 12b and 13 showed the highest binding affinity with CDOCKER energy score, while showed the lowest IC50 values against three types of cancer cell lines. It is worth to mention that, compounds 2e, 7a, 12b and 13 showed comparable inhibition activity to the reference drug, while compounds 4 and 12a showed a more potent inhibition activity than Doxorubicin.

  11. In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

    Directory of Open Access Journals (Sweden)

    A. G. Nerkar

    2009-01-01

    Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

  12. Quinolone resistance: much more than predicted

    Directory of Open Access Journals (Sweden)

    Alvaro eHernandez

    2011-02-01

    Full Text Available Since quinolones are synthetic antibiotics, it was predicted that mutations in target genes would be the only mechanism through which resistance could be acquired, because there will not be quinolone resistance genes in nature. Contrary to this prediction, a variety of elements ranging from efflux pumps, target-protecting proteins and even quinolone-modifying enzymes have been shown to contribute to quinolone resistance. The finding of some of these elements in plasmids indicates that quinolone resistance can be transferable. As a result, there has been a developing interest on the reservoirs for quinolone resistance genes and on the potential risks associated with the use of these antibiotics in non-clinical environments. As a matter of fact, plasmid-encoded, quinolone-resistance qnr genes originated in the chromosome of aquatic bacteria, thus the use of quinolones in fish farming might constitute a risk for the emergence of resistance. Failure to predict the development of quinolone resistance reinforces the need of taking into consideration the wide plasticity of biological systems for future predictions. This plasticity allows pathogens to deal with toxic compounds, including those with a synthetic origin as quinolones.

  13. Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship.

    Science.gov (United States)

    Roohbakhsh, Ali; Iranshahy, Milad; Iranshahi, Mehrdad

    2016-01-01

    The anti-cancer properties of liquorice have been attributed, at least in part, to glycyrrhizin (GL). However, GL is not directly absorbed through the gastrointestinal tract. It is hydrolyzed to 18-β-glycyrrhetinic acid (GA), the pharmacologically active metabolite, by human intestinal microflora. GA exhibits remarkable cytotoxic and anti-tumor properties. The pro-apoptotic targets and mechanisms of action of GA have been extensively studied over the past decade. In addition, GA is an inexpensive and available triterpene with functional groups (COOH and OH) in its structure, which make it an attractive lead compound for medicinal chemists to prepare a large number of analogues. To date, more than 400 cytotoxic derivatives have been prepared on the basis of GA scaffold, including 128 cytotoxic derivatives with IC50 values less than 30 µM. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC50s ≤ 1 µM. Studies have shown that the introduction of a double bound at the C1-C2 position combined with an electronegative functional group, such as CN, CF3 or iodine at C2 position, and the oxidation of the hydroxyl group of C3 to the carbonyl group, significantly increased cytotoxicity. This review describes the cytotoxic and anti-tumor properties of GA and its derivatives, targets and mechanisms of action and provides insight into the structure-activity relationship of GA derivatives.

  14. The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential

    Science.gov (United States)

    Prieto-Davó, Alejandra; Dias, Tiago; Gomes, Sofia E.; Rodrigues, Sara; Parera-Valadez, Yessica; Borralho, Pedro M.; Pereira, Florbela; Rodrigues, Cecilia M. P.; Santos-Sanches, Ilda; Gaudêncio, Susana P.

    2016-01-01

    Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced, and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura, and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100 m from shore) and nearshore (< 100 m from shore) populations illustrates the importance of sampling offshore in order to isolate new and diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora, and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry. PMID:27774089

  15. Synthesis and Anticancer Activity of Some New S-Glycosyl and S-Alkyl 1,2,4-Triazinone Derivatives

    Directory of Open Access Journals (Sweden)

    Hosam A. Saad

    2011-07-01

    Full Text Available A series of S-glycosyl and S-alkyl derivatives of 4-amino-3-mercapto-6-(2-(2-thienylvinyl-1,2,4-triazin-5(4H-one (1 were synthesized using different halo compounds such as preacetylated sugar bromide, 4-bromobutylacetate, 2-acetoxyethoxy-methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, allyl bromide, propargyl bromide, phthalic and succinic acids in POCl3. The structures of the synthesized compounds have been deduced from their elemental analysis and spectral (IR, 1H-NMR, and 13C-NMR data. Some of the synthesized compounds were screened as anticancer agents. Significant anticancer activities were observed in vitro for some members of the series, and compounds 4-Amino-3-(3-hydroxypropylthio-6-(2-(2-thienylvinyl-1,2,4-triazin-5(4H-one (12 and 3-(4-Oxo-3-(2-(2-thienylvinyl-4H-[1,3,4]thiadiazolo-[2,3-c][1,2,4]tr-iazin-7-ylpropanoic acid (18 are active cytotoxic agents against different cancer cell lines.

  16. Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents.

    Science.gov (United States)

    Song, Yaping; Xin, Zhengyuan; Wan, Yumeng; Li, Jiabin; Ye, Boping; Xue, Xiaowen

    2015-01-27

    A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 μM against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase. PMID:25506809

  17. A “Double-Edged” Scaffold: Antitumor Power within the 
Antibacterial Quinolone

    Science.gov (United States)

    Bisacchi, Gregory S.; Hale, Michael R.

    2016-01-01

    In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today’s predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents. PMID:26695512

  18. Quinolone resistance in the food chain.

    Science.gov (United States)

    Fàbrega, Anna; Sánchez-Céspedes, Javier; Soto, Sara; Vila, Jordi

    2008-04-01

    Antimicrobials are used in pet animals and in animal husbandry for prophylactic and therapeutic reasons and also as growth promoters, causing selective pressure on bacteria of animal origin. The impact of quinolones or quinolone-resistant bacteria on the management of human infections may be associated with three different scenarios. (i) Quinolone-resistant zoonotic bacterial pathogens are selected and food is contaminated during slaughter and/or preparation. (ii) Quinolone-resistant bacteria non-pathogenic to humans are selected in the animal. When the contaminated food is ingested, the bacteria may transfer resistance determinants to other bacteria in the human gut (commensal and potential pathogens). And (iii) quinolones remain in residues of food products, which may allow the selection of antibiotic-resistant bacteria after the food is consumed. In this review, we analyse the abovementioned aspects, emphasising the molecular basis of quinolone resistance in Escherichia coli, Salmonella spp. and Campylobacter spp. PMID:18308515

  19. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents.

    Science.gov (United States)

    Nagender, P; Naresh Kumar, R; Malla Reddy, G; Krishna Swaroop, D; Poornachandra, Y; Ganesh Kumar, C; Narsaiah, B

    2016-09-15

    A series of novel pyrazolo[3,4-b]pyridine based target compounds were synthesized starting from the key intermediate ethyl 2-(3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetate 5 on reaction with hydrazine hydrate followed by reaction with different aldehydes, acid chlorides and isothiocyanates to form hydrazones 7, oxadiazoles 8, 1,2,4 triazoles 10 and thiadiazoles 11 respectively in high yield. All the final compounds were screened for anticancer activity against four human cancer cell lines. Among them, 1,2,4 triazole derivatives showed promising activity and compound 10d is identified as a lead molecule. PMID:27528432

  20. Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors.

    Science.gov (United States)

    Kalirajan, R; Kulshrestha, Vivek; Sankar, S; Jubie, S

    2012-10-01

    A series of 9-anilinoacridines substituted with oxazine derivatives were synthesized to evaluate their antioxidant and anticancer activity against Daltons Lymphoma Ascites (DLA) cell growth by in vitro method. It was revealed that these conjugates exhibited significant antioxidant and anticancer activity (inhibition of DLA cell proliferation). Among these agents, compounds 5a, 5h, 5i, 5j were the most cytotoxic with CTC(50) value of 140-250 μg/mL. The docking studies of the synthesized compounds were performed towards the key Topoisomerase II (1QZR) by using Schrodinger Maestro 9.2 version. The oxazine substituted 9-anilinoacridine derivatives 5a, 5h, 5i, 5j have significant anticancer activity as topoisomerase II inhibitors. PMID:22982526

  1. Phenolic acid composition, antiatherogenic and anticancer potential of honeys derived from various regions in Greece.

    Directory of Open Access Journals (Sweden)

    Eliana Spilioti

    Full Text Available The phenolic acid profile of honey depends greatly on its botanical and geographical origin. In this study, we carried out a quantitative analysis of phenolic acids in the ethyl acetate extract of 12 honeys collected from various regions in Greece. Our findings indicate that protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid and p-coumaric acid are the major phenolic acids of the honeys examined. Conifer tree honey (from pine and fir contained significantly higher concentrations of protocatechuic and caffeic acid (mean: 6640 and 397 µg/kg honey respectively than thyme and citrus honey (mean of protocatechuic and caffeic acid: 437.6 and 116 µg/kg honey respectively. p-Hydroxybenzoic acid was the dominant compound in thyme honeys (mean: 1252.5 µg/kg honey. We further examined the antioxidant potential (ORAC assay of the extracts, their ability to influence viability of prostate cancer (PC-3 and breast cancer (MCF-7 cells as well as their lowering effect on TNF- α-induced adhesion molecule expression in endothelial cells (HAEC. ORAC values of Greek honeys ranged from 415 to 2129 µmol Trolox equivalent/kg honey and correlated significantly with their content in protocatechuic acid (p<0.001, p-hydroxybenzoic acid (p<0.01, vanillic acid (p<0.05, caffeic acid (p<0.01, p-coumaric acid (p<0.001 and their total phenolic content (p<0.001. Honey extracts reduced significantly the viability of PC-3 and MCF-7 cells as well as the expression of adhesion molecules in HAEC. Importantly, vanillic acid content correlated significantly with anticancer activity in PC-3 and MCF-7 cells (p<0.01, p<0.05 respectively. Protocatechuic acid, vanillic acid and total phenolic content correlated significantly with the inhibition of VCAM-1 expression (p<0.05, p<0.05 and p<0.01 respectively. In conclusion, Greek honeys are rich in phenolic acids, in particular protocatechuic and p-hydroxybenzoic acid and exhibit significant antioxidant, anticancer and

  2. Design, synthesis and biological evaluation of novel pyridine derivatives as anticancer agents and phosphodiesterase 3 inhibitors

    Science.gov (United States)

    Abadi, Ashraf H.; Ibrahim, Tamer M.; Abouzid, Khaled M.; Lehmann, Jochen; Tinsley, Heather N.; Gary, Bernard D.; Piazza, Gary A.

    2016-01-01

    Two series of 4,6-diaryl-2-imino-1,2-dihydropyridine-3-carbonitriles and their isosteric 4,6-diaryl-2- oxo-1,2-dihydropyridine-3-carbonitriles were synthesized through a combinatorial approach. The prepared analogues were evaluated for their in vitro capacity to inhibit PDE3A and the growth of the human HT-29 colon adenocarcinoma tumor cell line. Compound 6-(4-bromophenyl)-4-(2-ethoxyphenyl)-2- imino-1,2-dihydropyridine-3-carbonitrile (Id) exhibited the strongest PDE3 inhibition when cGMP but not cAMP is the substrate with a IC50of 27 μM, which indicates a highly selective mechanism of enzyme inhibition. On the other hand, compound 6-(1,3-benzodioxol-5-yl)-4-(2-ethoxyphenyl)-2-imino-1,2- dihydropyridine-3-carbonitrile (Ii) was the most active in inhibiting colon tumor cell growth with a IC50 of 3 μM. The electronic effects, steric effects and conformational aspects of Id seem to be the most crucial for the PDE3 inhibition. Meanwhile, steric factors and the H-bonding capability seem to be the most important factors for tumor cell growth inhibitory activity. Conversely, there is no direct correlation between PDE3 inhibition and anticancer activity for the prepared compounds. An in silico docking experiment indicates the potential involvement of other potential molecular targets such as PIM-1 kinase to explain its tumor cell growth inhibitory activity. PMID:19628397

  3. Greco-Arab and Islamic Herbal-Derived Anticancer Modalities: From Tradition to Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Hilal Zaid

    2012-01-01

    Full Text Available The incidence of cancer is increasing in the developed countries and even more so in developing countries parallel to the increase in life expectancy. In recent years, clinicians and researchers advocate the need to include supportive and palliative care since the establishment of the diagnosis and throughout the duration of treatment, with the goal of improving patients' quality of life. This patient-centered approach in supportive care is also shared by various traditional and complementary medicine approaches. Traditional Arab-Islamic medicine offers a variety of therapeutic modalities that include herbal, nutritional, and spiritual approaches. Physicians and scholars, such as Avicenna (980–1037, Rhazes (965–915, Al Zahrawi (936–1013, and Ibn al Nafis (1218–1288 referred to cancer etiology in various medicinal texts and suggested both preventive and therapeutic remedies to alleviate suffering. This review presents research data related to the anticancer activities of herbs used in Arab-Islamic medicine and allude to their potential role in improving the quality of life of cancer patients.

  4. Anticancer and antimicrobial activity of mangrove derived fungi Hypocrea lixii VB1

    Institute of Scientific and Technical Information of China (English)

    B.ValentinBhimba; D.A.AgnelDeforaFranco; JibiMerinMathew; GeenaMaryJose; ElsaLyciasJoel; M.Thangaraj

    2012-01-01

    AIM:Mangrove is one of the oldest living tree species and its leaves are among the most extensively studied botanicals in use today.Scientific research throughout the world has found evidence to support the fact that its foliar extracts have great potential against human microbial pathogens.This study highlights the isolation of foliar fungi from Rhizophora mucronata,Avicenna officialis and Avicenna marina.METHOD:It was isolated in Sabouroud's Dextrose Agar and mass cultivation was done in Sabouroud's Dextrose broth.RESULTS:The ethyl acetate extract showed maximum antibacterial activity which inturn checked for different concentration against bacterial pathogens and anticancer activity for Hep2 and MCF-7cell line in vitro.The DNA was isolated from the fungi and the ITS region of 5.8 s RNA was sequenced and assigned to new species as they are separated from the type strains phylogenetic neighbors by sequence similarities.CONCLUSION:This preliminary screening of fungal endophytes revealed their potential to yield potent bioactive compounds for drug discovery programmes.

  5. The disulfide compound α-lipoic acid and its derivatives: A novel class of anticancer agents targeting mitochondria.

    Science.gov (United States)

    Dörsam, Bastian; Fahrer, Jörg

    2016-02-01

    The endogenous disulfide α-lipoic acid (LA) is an essential mitochondrial co-factor. In addition, LA and its reduced counterpart dihydro lipoic acid form a potent redox couple with antioxidative functions, for which it is used as dietary supplement and therapeutic. Recently, it has gained attention due to its cytotoxic effects in cancer cells, which is the key aspect of this review. We initially recapitulate the dietary occurrence, gastrointestinal absorption and pharmacokinetics of LA, illustrating its diverse antioxidative mechanisms. We then focus on its mode of action in cancer cells, in which it triggers primarily the mitochondrial pathway of apoptosis, whereas non-transformed primary cells are hardly affected. Furthermore, LA impairs oncogenic signaling and displays anti-metastatic potential. Novel LA derivatives such as CPI-613, which target mitochondrial energy metabolism, are described and recent pre-clinical studies are presented, which demonstrate that LA and its derivatives exert antitumor activity in vivo. Finally, we highlight clinical studies currently performed with the LA analog CPI-613. In summary, LA and its derivatives are promising candidates to complement the arsenal of established anticancer drugs due to their mitochondria-targeted mode of action and non-genotoxic properties. PMID:26604131

  6. Preparation, characterization and in vitro evaluation of sterically stabilized liposome containing a naphthalenediimide derivative as anticancer agent.

    Science.gov (United States)

    Parise, Amelia; Milelli, Andrea; Tumiatti, Vincenzo; Minarini, Anna; Neviani, Paolo; Zuccari, Guendalina

    2015-01-01

    The aim of this study was to incorporate a new naphthalenediimide derivative (AN169) with a promising anticancer activity into pegylated liposomes to an extent that allows its in vitro and in vivo testing without use of toxic solvent. AN169-loaded liposomes were prepared using the thin-film hydration method and characterized for size, polydispersity index, drug content and drug release. We examined their lyophilization ability in the presence of cryoprotectants (trehalose, sucrose and lysine) and the long-term stability of the lyophilized products stored at 4 °C for 3 and 6 months by particle size changes and drug leakage. AN169 was successfully loaded into liposomes with an entrapment efficiency of 87.3 ± 2.5%. The hydrodynamic diameter of these liposomes after sonication was ∼ 145 nm with a high degree of monodispersity. Trehalose was found to be superior to the other lyoprotectants. In particular, trehalose 1:10 lipid:cryoprotectant molar ratio may provide stable lyophilized liposomes with the conservation of physicochemical properties upon freeze-drying and long-term storage conditions. We also assessed their in vitro antitumor activity in human cancer cell lines (HTLA-230 neuroblastoma, Mel 3.0 melanoma, OVCAR-3 ovarian carcinoma and SV620 prostate cancer cells). However, only after 72 h incubation, loaded liposomes showed almost the same IC50 as free AN169. In conclusion, we developed a stable lyophilized liposomal formulation for intravenous administration of AN169 as anticancer drug, with the advantage of avoiding the use of potentially toxic solubilizing agents for future in vivo experiments. PMID:24286206

  7. New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Morin, Nathalie; Bruneau, Julie; Fortin, Sebastien; Brasseur, Kevin; Leblanc, Valerie; Asselin, Eric; Berube, Gervais

    2015-01-01

    Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective "natural" or "semisynthetic" anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC. PMID:25675439

  8. Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

    OpenAIRE

    Yanmin Huang; Jianguo Cui; Sijing Chen; Qifu Lin; Huacan Song; Chunfang Gan; Bin Su; Aimin Zhou

    2014-01-01

    Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mecha...

  9. Synthesis and evaluation of nitrate derivatives of colchicine as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Li Hong Shen; Ya Li; Da Hai Zhang; Yi Sheng Lai; Li Jie Liu

    2011-01-01

    To search for more potent antitumor agent, a series of novel nitric oxide-donating colchicine (Col) derivatives (6a-f, 8a and b) were synthesized by coupling nitrates with N-methyl colchiceinamide. Their cytotoxicity against four human cancer cell lines in vitro were evaluated by MTT assay. It was found that many of the derivatives displayed significant activity, particularly, compounds 6c, 8a and 8b showed more potent cytotoxic activities than Col.

  10. A General Synthetic Procedure for 2-chloromethyl-4(3H-quinazolinone Derivatives and Their Utilization in the Preparation of Novel Anticancer Agents with 4-Anilinoquinazoline Scaffolds

    Directory of Open Access Journals (Sweden)

    Ying-Lan Zhao

    2010-12-01

    Full Text Available In our ongoing research on novel anticancer agents with 4-anilinoquinazoline scaffolds, a series of novel 2-chloromethyl-4(3H-quinazolinones were needed as key intermediates. An improved one-step synthesis of 2-chloromethyl-4(3H-quinazolinones utilizing o-anthranilic acids as starting materials was described. Based on it, 2-hydroxy-methyl-4(3H-quinazolinones were conveniently prepared in one pot. Moreover, two novel 4-anilinoquinazoline derivatives substituted with chloromethyl groups at the 2-position were synthesized and showed promising anticancer activity in vitro.

  11. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  12. Polycyclic Aromatic Compounds as Anticancer Agents: Synthesis and Biological Evaluation of Methoxy Dibenzofluorene Derivatives

    Directory of Open Access Journals (Sweden)

    Bimal Krishna Banik

    2014-08-01

    Full Text Available Synthesis of a new methoxy dibenzofluorene through alkylation, cyclodehydration and aromatization in a one-pot operation is achieved for the first time. Using this hydrocarbon, a few derivatives are prepared through aromatic nitration, catalytic hydrogenation, coupling reaction with a side chain and reduction. The benzylic position of this hydrocarbon with the side chain is oxidized and reduced. Some of these derivatives have demonstrated excellent antitumor activities in vitro. This study confirms antitumor activity depends on the structures of the molecules.

  13. Evaluation of quinolone antibacterial consumption

    Directory of Open Access Journals (Sweden)

    E. P. Bernaz

    2016-08-01

    Full Text Available Quinolones are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected and as first-line therapy is recommended. To determine the place, compare and analyze the use of quinolone antibacterial in the most important departments of EMI during 2009 to 2014 and to assess their results for improvement of patients treatment quality was designed this study. In the evaluated period consumption of quinolone antibacterial in EMI recorded a decline from 91 to 46 DDD/1000 or by 49.45%, in IC departaments from 338.6 to 132.07 or by 61%, and vice versa in SSOT departments an increase from 41.28 to 57.59 DDD/1000 or by 31.51%. Medium annual consumption in all institution recorded 63.03 DDD/1000, respectvely 174.90 in IC and 45.10 in SSOT departments. In 2014 IC departments recorded 2439.8 lei per DDD/1000, that was 8.72 times more than cost of 279.9 lei in SSOT departments and 7.51 times than 324.96 lei per DDD/1000 in all EMI. The yearly medium in EMI is around the same with all other international hospitals of 66.13 DDD/1000 and by 27.23% higher than 49.54 DDD/1000 recorded in large acute Australian public hospitals. The obtained results will be an important data for optimization in planning annual hospital necessities and rational antimicrobial prescribing as well as suggest the idea for expansion development and support antimicrobial stewardship initiatives.

  14. Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

    International Nuclear Information System (INIS)

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  15. Synthesis and biological evaluation of nitric oxide-releasing matrine derivatives as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of furoxan-based nitric oxide-releasing matrine derivatives(10a-f) were synthesized.The biological evaluation showed that compounds 10a,10b,10e and 10f had stronger cytotoxic activities than 5-fluorouracil against human hepatoma cells(HepG2) in vitro.

  16. Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

    Science.gov (United States)

    Taşdemir, Demet; Karaküçük-İyidoğan, Ayşegül; Ulaşli, Mustafa; Taşkin-Tok, Tuğba; Oruç-Emre, Emİne Elçİn; Bayram, Hasan

    2015-02-01

    A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. PMID:25399965

  17. Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Yanmin Huang

    2014-03-01

    Full Text Available Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR generated in the studies is valuable for the design of novel chemotherapeutic agents.

  18. Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions

    Directory of Open Access Journals (Sweden)

    George P. Dinos

    2016-06-01

    Full Text Available Chloramphenicol (CAM is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM.

  19. [Vinflunine: a new anti-cancer fluorinated agent derived from Vinca-alkaloids].

    Science.gov (United States)

    Jacquesy, J C; Jouannetaud, M P

    2005-01-01

    Reaction in superacid HF-SbF5 in the presence of CCl4 of vinorelbine yields (4'R)-20',20'difluoro-3',4'dihydrovinorelbine (vinflunine), whereas vinblastine or anhydrovinblastine give the difluoro analog. The reaction implies a 20' chloro derivative as intermediate which undergoes hydrid abstraction at C20' followed by halogen exchange. Vinflunine is presently in phase III experimentation for treatment of bladder cancer and non small lung cancer. PMID:15803098

  20. Anti-cancer agents derived from solid-state fermented Antrodia camphorata mycelium.

    Science.gov (United States)

    Yen, I-Chuan; Yao, Chen-Wen; Kuo, Mao-Tien; Chao, Chen-Liang; Pai, Chien-Yi; Chang, Wen-Liang

    2015-04-01

    Three new ubiquinone derivatives, antrocamol LT1, antrocamol LT2, and antrocamol LT3, along with two known compounds, were isolated from Antrodia camphorata (Polyporaceae) mycelium. The structures of these compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analyses. These ubiquinones exhibited selective cytotoxicities against five human cancer cell lines (CT26, A549, HepG2, PC3 and DU-145) with IC50 values ranging from 0.01 to 1.79μΜ. PMID:25721423

  1. Plant derived substances with anti-cancer activity: from folklore to practice

    OpenAIRE

    Marcelo eFridlender; Yoram eKapulnik; Hinanit eKoltai

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early 19th century. This trend led to the discovery of different active compounds that are derived from plants. I...

  2. Plant derived substances with anti-cancer activity: from folklore to practice

    OpenAIRE

    Fridlender, Marcelo; Kapulnik, Yoram; Koltai, Hinanit

    2015-01-01

    Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years. It is estimated that 70–95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century. This trend led to the discovery of different active compounds that are derived from pla...

  3. The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives

    Directory of Open Access Journals (Sweden)

    Liang Liu

    2011-12-01

    Full Text Available Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE, protopanaxadiol (PPD-type, protopanaxatriol (PPT-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1, compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S-dihydroprotopanaxadiol (2 > PPD (1 > 20(S-Rh2 > 20(R-Rh2 ≈ 20(R-Rg3 ≈ 20(S-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells.

  4. Nitro-oxidative Stress Is Involved in Anticancer Activity of 17β-Estradiol Derivative in Neuroblastoma Cells.

    Science.gov (United States)

    Gorska, Magdalena; Kuban-Jankowska, Alicja; Milczarek, Ryszard; Wozniak, Michal

    2016-04-01

    Neuroblastoma is one of the most common childhood malignancies and the primary cause of death from pediatric cancer. Derivatives of 17β-estradiol, 2-methoxyestradiol, as well as selective estrogen receptor modulators, such as fulvestrant, are novel potentially active anticancer agents. In particular, 2-methoxyestradiol is effective in treatment of numerous malignancies, including breast and prostate cancer, Ewing sarcoma, and osteosarcoma. Herein, we treated neuroblastoma SH-SY5Y cells with physiologically and pharmacologically relevant concentrations of 2-methoxyestradiol. We used flow cytometry in order to determine cell viability, cell death, level of nitric oxide and mitochondrial membrane potential. We demonstrated that at pharmacologically relevant concentrations, 2-methoxyestradiol results in induction of apoptosis of neuroblastoma SH-SY5Y cells via nitric oxide generation and reduction of mitochondrial membrane potential. Based on the obtained data, we propose that 2-methoxyestradiol may be a natural modulator of cancer cell death and survival through nitro-oxidative stress-dependent mechanisms. Moreover, the results confirm the efficiency of 2-methoxyestradiol in treatment of neuroblastoma.

  5. Nitro-oxidative Stress Is Involved in Anticancer Activity of 17β-Estradiol Derivative in Neuroblastoma Cells.

    Science.gov (United States)

    Gorska, Magdalena; Kuban-Jankowska, Alicja; Milczarek, Ryszard; Wozniak, Michal

    2016-04-01

    Neuroblastoma is one of the most common childhood malignancies and the primary cause of death from pediatric cancer. Derivatives of 17β-estradiol, 2-methoxyestradiol, as well as selective estrogen receptor modulators, such as fulvestrant, are novel potentially active anticancer agents. In particular, 2-methoxyestradiol is effective in treatment of numerous malignancies, including breast and prostate cancer, Ewing sarcoma, and osteosarcoma. Herein, we treated neuroblastoma SH-SY5Y cells with physiologically and pharmacologically relevant concentrations of 2-methoxyestradiol. We used flow cytometry in order to determine cell viability, cell death, level of nitric oxide and mitochondrial membrane potential. We demonstrated that at pharmacologically relevant concentrations, 2-methoxyestradiol results in induction of apoptosis of neuroblastoma SH-SY5Y cells via nitric oxide generation and reduction of mitochondrial membrane potential. Based on the obtained data, we propose that 2-methoxyestradiol may be a natural modulator of cancer cell death and survival through nitro-oxidative stress-dependent mechanisms. Moreover, the results confirm the efficiency of 2-methoxyestradiol in treatment of neuroblastoma. PMID:27069147

  6. Synthesis, evaluation and QSAR studies of 16-(4 & 3,4-substituted) benzylidene androstene derivatives as anticancer agents.

    Science.gov (United States)

    Dubey, S; Kaur, P; Jindal, D P; Satyanarayan, Y D; Piplani, P

    2008-05-01

    In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antipoliferative activity against cancer cells and developing their QSAR models, series of 4-nitro, 4-isopropyl, 4-methoxy and 3,4-dimethoxy substituted benzylidene androst-5-ene derivatives were synthesized. The selected compounds were evaluated for antineoplastic activity against a panel of three human cell lines-breast, CNS and lungs at NCI, Bethesda, USA. The results presented herein reports that compounds 7, 9, 10, 15,16, 18, 20-25, 30, 32-36 and 44 have been found to be active anticancer agents. The QSAR of 20 compounds was performed separately for each cell line and best-fit QSAR models are developed. The QSAR models obtained have shown significant correlations (r(2) range: 0.9163 to 0.8164) and good predictive performance (q(2) range: 0.8499- 0.6320). The validation of models has also been performed using the test set of compounds 5, 15 and 44.

  7. Synthesis and biological evaluation of nitric oxide-releasing sixalkoxyl biphenyl derivatives as anticancer agents

    Institute of Scientific and Technical Information of China (English)

    Xiang Wen Kong; Yi Hua Zhang; Li Dai; Hui Ji; Yi Sheng Lai; Si Xun Peng

    2008-01-01

    A series of novel nitric oxide-donating sixalkoxyl biphenyl derivatives (14a-i)were synthesized by coupling furoxan with alkoxyl biphenyl skeleton using amino acids as the spacers,and their cytotoxicity against HepG2 cells in vitro were evaluated by MTr method.It was found that 14c,14d,14f,14i,14j and 14k showed more potent cytotoxic activities than control 5-fluorouracil.NO release assay of target compounds indicated that the maximum amount of NO released by most active compounds 14c and 14j was about 6 x 10-2μmol/L,whereas 14a and 14h with very weak activity only released NO of 1 x 10-μmol/L.

  8. Clinical status of anti-cancer agents derived from marine sources.

    Science.gov (United States)

    Singh, Ram; Sharma, Mukul; Joshi, Penny; Rawat, Diwan S

    2008-08-01

    The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds. PMID:18690825

  9. Discovery of indeno[1,2-b]quinoxaline derivatives as potential anticancer agents.

    Science.gov (United States)

    Tseng, Chih-Hua; Chen, You-Ren; Tzeng, Cherng-Chyi; Liu, Wangta; Chou, Chon-Kit; Chiu, Chien-Chih; Chen, Yeh-Long

    2016-01-27

    We have synthesized certain indeno[1,2-b]quinoxaline derivatives for antiproliferative evaluation. Among them, 11-{[3-(dimethylamino)propoxy]imino}-N-[3-(dimethylamino) propyl]-11H-indeno[1,2-b]quinoxaline-6-carboxamide (10a) was active against the growth of MDA-MB231, PC-3, and Huh-7 with IC50 values of 0.87 (selectivity index, SI = 36.22), 0.82 (SI = 38.43), and 0.64 μM (SI = 49.23) respectively. Compound 10a was inactive against the growth of normal human fetal lung fibroblast cell line (MRC-5) with an IC50 value of 31.51 μM. Its analogs, 10b and 10c, were also active against the growth of MB231, PC-3, and Huh-7 with IC50 values of <1.0 μM in each case. Our results have also indicated compounds 10a-10c exhibited comparable inhibitory activities against topo I and topo II with the positive compound 2 at a concentration of 10 μM. Mechanism studies indicated that compound 10a induced cell cycle arrest at S phase via activation of caspase-3, -7 and an increase in the protein expression of Bad and Bax but a decrease in expression of Bcl-2 and PARP, which consequently cause cell death. In addition, compound 10a attenuated the levels of phosphorylated Src, Akt-1, and Akt-2 protein levels but did not affect the total protein expression of Akt. We have also implanted human hepatocellular carcinoma cells into the yolk sac of zebrafish larvae and incubated larvae with various concentrations of 10a. Our results of the zebrafish xenograft assay confirmed the anti-tumor effect of 10ain vivo.

  10. Synthesis of 1-benzyl-3-(5-hydroxymethyl-2-furyl)selenolo[3,2-c]pyrazole derivatives as new anticancer agents.

    Science.gov (United States)

    Chou, Li-Chen; Huang, Li-Jiau; Hsu, Mei-Hua; Fang, Mei-Chi; Yang, Jai-Sing; Zhuang, Shi-Hong; Lin, Hui-Yi; Lee, Fang-Yu; Teng, Che-Ming; Kuo, Sheng-Chu

    2010-04-01

    As part of our continuing search for potential anticancer drug candidates among YC-1 analogs, 1, 3-disubstituted selenolo[3,2-c]pyrazole derivatives were synthesized and evaluated for their cytotoxicity against NCI-H226 non-small cell lung cancer and A-498 renal cancer cell lines. Significant cytotoxicity was observed in 3-(5-hydroxymethyl-2-furyl) derivatives (2, 33, 36 and 37). Among them, compound 2 was found to have the most potent activity. The mode of action of compound 2 seems to differ from those of the 175 anticancer agents listed in NCI's standard database and resembles that of YC-1. Thus, we recommend that compound 2 should be developed further as new drug candidate for treatment of non-small cell lung cancer and renal cancer. PMID:20097456

  11. A Survey of Marine Natural Compounds and Their Derivatives with Anti-Cancer Activity Reported in 2011

    OpenAIRE

    Marc Diederich; Claudia Cerella; Marie-Hélène Teiten; Wamtinga Richard Sawadogo; Marc Schumacher; Mario Dicato

    2013-01-01

    Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study...

  12. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  13. Cationic Antimicrobial Peptides Derived from Crocodylus siamensis Leukocyte Extract, Revealing Anticancer Activity and Apoptotic Induction on Human Cervical Cancer Cells.

    Science.gov (United States)

    Theansungnoen, Tinnakorn; Maijaroen, Surachai; Jangpromma, Nisachon; Yaraksa, Nualyai; Daduang, Sakda; Temsiripong, Theeranan; Daduang, Jureerut; Klaynongsruang, Sompong

    2016-06-01

    Known antimicrobial peptides KT2 and RT2 as well as the novel RP9 derived from the leukocyte extract of the freshwater crocodile (Crocodylus siamensis) were used to evaluate the ability in killing human cervical cancer cells. RP9 in the extract was purified by a combination of anion exchange column and reversed-phase HPLC, and its sequence was analyzed by mass spectrometry. The novel peptide could inhibit Gram-negative Vibrio cholerae (clinical isolation) and Gram-positive Bacillus pumilus TISTR 905, and its MIC values were 61.2 µM. From scanning electron microscopy, the peptide was seen to affect bacterial surfaces directly. KT2 and RT2, which are designed antimicrobial peptides using the C. siamensis Leucrocin I template, as well as RP9 were chemically synthesized for investigation of anticancer activity. By Sulforhodamine B colorimetric assay, these antimicrobial peptides could inhibit both HeLa and CaSki cancer cell lines. The IC50 values of KT2 and RT2 for HeLa and CaSki cells showed 28.7-53.4 and 17.3-30.8 µM, while those of RP9 were 126.2 and 168.3 µM, respectively. Additionally, the best candidate peptides KT2 and RT2 were used to determine the apoptotic induction on cancer cells by human apoptosis array assay. As a result, KT2 and RT2 were observed to induce apoptotic cell death in HeLa cells. Therefore, these results indicate that KT2 and RT2 with antimicrobial activity have a highly potent ability to kill human cervical cancer cells. PMID:27129462

  14. Anticancer efficacy of a nitric oxide-modified derivative of bifendate against multidrug-resistant cancer cells.

    Science.gov (United States)

    Ren, Zhiguang; Gu, Xiaoke; Lu, Bin; Chen, Yaqiong; Chen, Guojiang; Feng, Jiannan; Lin, Jizhen; Zhang, Yihua; Peng, Hui

    2016-06-01

    The development of multidrug resistance (MDR) not only actively transports a wide range of cytotoxic drugs across drug transporters but is also a complex interaction between a number of important cellular signalling pathways. Nitric oxide donors appear to be a new class of anticancer therapeutics for satisfying all the above conditions. Previously, we reported furoxan-based nitric oxide-releasing compounds that exhibited selective antitumour activity in vitro and in vivo. Herein, we demonstrate that bifendate (DDB)-nitric oxide, a synthetic furoxan-based nitric oxide-releasing derivative of bifendate, effectively inhibits the both sensitive and MDR tumour cell viability at a comparatively low concentration. Interestingly, the potency of DDB-nitric oxide is the independent of inhibition of the functions and expressions of three major ABC transporters. The mechanism of DDB-nitric oxide appears to be in two modes of actions by inducing mitochondrial tyrosine nitration and apoptosis, as well as by down-regulating HIF-1α expression and protein kinase B (AKT), extracellular signal-regulated kinases (ERK), nuclear factor κB (NF-κB) activation in MDR cells. Moreover, the addition of a typical nitric oxide scavenger significantly attenuated all the effects of DDB-nitric oxide, indicating that the cytotoxicity of DDB-nitric oxide is as a result of higher levels of nitric oxide release in MDR cancer cells. Given that acquired MDR to nitric oxide donors is reportedly difficult to achieve and genetically unstable, compound like DDB-nitric oxide may be a new type of therapeutic agent for the treatment of MDR tumours.

  15. Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

    Directory of Open Access Journals (Sweden)

    Maria P. Crespo-Ortiz

    2012-01-01

    Full Text Available Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.

  16. Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Supuran, Claudiu T; Scozzafava, Andrea;

    2002-01-01

    The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux....

  17. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

    Science.gov (United States)

    Klopman, G; Li, J Y; Wang, S; Pearson, A J; Chang, K; Jacobs, M R; Bajaksouzian, S; Ellner, J J

    1994-08-01

    The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

  18. Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model.

    Science.gov (United States)

    Sittaramane, Vinoth; Padgett, Jihan; Salter, Philip; Williams, Ashley; Luke, Shauntelle; McCall, Rebecca; Arambula, Jonathan F; Graves, Vincent B; Blocker, Mark; Van Leuven, David; Bowe, Keturah; Heimberger, Julia; Cade, Hannah C; Immaneni, Supriya; Shaikh, Abid

    2015-11-01

    In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 μm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.

  19. Anti-cancer agents based on 4-(hetero)Ary1-1,2,5-oxadiazol-3-yl Amino derivatives and a method of making

    Science.gov (United States)

    Gakh, Andrei A.; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A.; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V.

    2013-01-29

    The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. ##STR00001## In particular, the invention relates N-substituted derivatives of 4-(hetero)aryl-1,2,5-oxadiazol-3-yl amines having the structural Formula (I) and (II), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. Meaning of R1 and R2 in the Formula (I) and (II) are defined in claim 1. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  20. Synthesis, biological evaluation and molecular docking studies of some novel cyclopropane carbohydrazide derivatives as potential anticancer agents

    Indian Academy of Sciences (India)

    PONNAPALLI VEERABHADRA SWAMY; PULLAIAH CHINA KAMBHAMPATI; KOTHAPALLI BONNOTH CHANDRASEKHAR; GUGULOTHU THIRUPATHI; POMBALA SUJITHA; CHITYAL GANESH KUMAR; VEERAMACHANENI GANESH KUMAR

    2016-06-01

    The synthesis of novel series of cyclopropane carbohydrazides is described via Knoevenagel condensationof 2-furfuraldehyde with malonic acid in five steps. Condensation of the key intermediate 2-(furan-2-yl)cyclopropanecarbohydrazide (4) with heteroaryl/aryl aldehydes (a-t) in presence of ZnO NP in ethanolresulted in substituted N- hetero/arylidene-2-(furan-2-yl) cyclopropane carbohydrazides (5a-t). These compoundswere screened for their anticancer activity against a panel of four cancer cell lines and four compoundsshowed promising activity at micromolar concentration against all the tested cell lines with IC50 values rangingbetween 1.9-8.45μM. These compounds were further validated with in silico methods at the anticancer target,colchicine binding site.

  1. Novel Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins with Potent in Vitro and in Vivo Anticancer Activities.

    Science.gov (United States)

    Medellin, Derek C; Zhou, Qiong; Scott, Robert; Hill, R Matthew; Frail, Sarah K; Dasari, Ramesh; Ontiveros, Steven J; Pelly, Stephen C; van Otterlo, Willem A L; Betancourt, Tania; Shuster, Charles B; Hamel, Ernest; Bai, Ruoli; LaBarbera, Daniel V; Rogelj, Snezna; Frolova, Liliya V; Kornienko, Alexander

    2016-01-14

    Docking studies of tubulin-targeting C2-substituted 7-deazahypoxanthine analogues of marine alkaloid rigidins led to the design and synthesis of compounds containing linear C2-substituents. The C2-alkynyl analogue was found to have double- to single-digit nanomolar antiproliferative IC50 values and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations. These results provide impetus and further guidance for the development of these rigidin analogues as anticancer agents. PMID:26641132

  2. Design, synthesis and anticancer activity of new 3-cyano-2 (1H -pyridone and 3-cyanopyridine-2-(1H-thione derivatives

    Directory of Open Access Journals (Sweden)

    E. A. Abdel Motaal

    2015-06-01

    Full Text Available The main objective of the present research study is to synthesize some novel chalcone, cyanoacetohydrazone, enaminone, 3-cyano-2(1H-pyridone and 3-cyanopyridine-2-(1H-thione derivatives and evaluate them for their anticancer effect. The novel chalcones 2a-c were achieved by Claisen-Schmidt condensation of appropriate benzaldehydes with ethanone derivative 1. Treatment of cyanoacetic acid hydrazide with ethanone derivative 1 yielded the correspondinghydrazone derivative 3. Condensation of ethanone derivative 1 with DMF-DMA afforded (E-3-(dimethylamino-1- (4- morpholinophenylprop-2-en-1-one 4. Heterocyclization of chalcones 2a-c with cyanothioacetamide yielded 2-thioxo-1,2-dihydropyridine-3-carbonitriles 7a-c. In a similar manner, cyclocondensation of chalcones 2a,b with cyanoacetamide afforded the corresponding 2-oxo-1,2-dihydropyridine-3-carbonitriles 8a,b. The Reaction of compound 2a with ethyl cyanoacetate furnished 2-oxo-1,2-dihydropyridine-3-carboxylate 12. The 2-oxo-4-phenyl-1,2-dihydro-pyridine-3,5-dicarbonitriles 14a,b were obtained by cyclization of cyano-acetohydrazone 3 with cinnamonitriles. The structures of the synthesized compounds were confirmed by elemental analysis, mass spectrometry, IR and 1H-NMR spectroscopy. The anticancer activity of the newly synthesized compounds was screened in vitro against Human lung carcinoma (A 549 cell line indicating that compounds 7b and 8a possess the most potent inhibitory effect against the human lung carcinoma cell line (A549.

  3. Proficiency study for quinolones in egg

    NARCIS (Netherlands)

    Berendsen, B.J.A.; Stolker, A.A.M.

    2008-01-01

    Studie naar het voorkomen van quinolonen in eieren, beschrijving van de testmaterialen, evaluatie van de toegepaste methoden, resultaten en discussieThe aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of quinolones i

  4. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  5. Progress in Synthesis of 4-Hydroxyquinoline Derivatives%4-羟基喹啉类化合物的合成研究进展

    Institute of Scientific and Technical Information of China (English)

    茆勇军; 何海军

    2014-01-01

    4-羟基喹啉类[4-hydroxyquinolines或4(1H)quinolones]化合物是一类重要的药物合成中间体,在抗疟、抗癌、抗菌、抗病毒、抗糖尿病等领域发挥重要作用。本文综述了4-羟基喹啉类衍生物的合成方法,包括热环合、碱环合和还原环合等。%4-Hydroxyquinoline [or 4(1H)quinolone] derivatives are important intermediates in pharmaceutical synthesis and play significant roles in antimalarial, anticancer, antibacterial, antiviral and antidiabetic. Progress in synthesis of 4-hydroxyquinoline derivatives, including thermal, basic and reductive cyclization methods, are summarized.

  6. The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Abdul Naeem

    2016-03-01

    Full Text Available Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites—the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1 mutation in the target site (gyrase and/or topoisomerase IV of quinolones; (2 plasmid-mediated resistance; and (3 chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV. In the case of

  7. Synthesis, quantitative structure-activity relationship and biological evaluation of 1,3,4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents.

    Science.gov (United States)

    Abdel Rahman, Doaa Ezzat

    2013-01-01

    Synthesis of 2,5-disubstituted-1,3,4-oxadiazole (2a-c), 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2(3H)-thione (4a-m) and 2-substituted thio-5-substituted-1,3,4-oxadiazole (5a, b) had been described. All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line. Compounds 2a-c, 4f and 5a exhibited potent cytotoxicity (IC(50) 1.3-2.0 µM) and selectivity against HT29 cancer cell line. Quantitative structure-activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.

  8. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    Science.gov (United States)

    Abd El-Karim, Somaia S; Anwar, Manal M; Mohamed, Neama A; Nasr, Tamer; Elseginy, Samia A

    2015-12-01

    This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.

  9. Quinolone-resistance in Salmonella is associated with decreased mRNA expression of virulence genes invA and avrA, growth and intracellular invasion and survival.

    Science.gov (United States)

    Wang, Yu-Ping; Li, Lin; Shen, Jian-Zhong; Yang, Fu-Jiang; Wu, Yong-Ning

    2009-02-01

    A variety of environmental factors, such as oxygen, pH, osmolarity and antimicrobial agents, modulate the expression of Salmonella pathogenicity islands (SPI) genes. This study investigated SPI-1 gene expression and the pathogenicity of quinolone-resistant Salmonella. mRNA expression levels of the invA and avrA genes, located in SPI-1, in quinolone-susceptible and quinolone-resistant Salmonella strains were determined using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Twenty-five quinolone-resistant Salmonella mutants were derived from quinolone-susceptible strains by multiple-passage selection through increasing concentrations of ciprofloxacin in vitro, while an additional 15 strains were quinolone-resistant Salmonella clinical isolates. Sequence analysis showed no gene deletion or point mutations of nine SPI-1 genes (including invA and avrA) occurred in either the selected or clinical quinolone-resistant strains, while a single gyrA point mutation (S83F) was observed in all 40 quinolone-resistant strains. The mRNA expression levels of invA and avrA were significantly decreased (P<0.005) in quinolone-resistant strains (clinically acquired or experimentally selected in vitro), compared to the quinolone-susceptible strains. The resistant strains also had a slower growth rate combined with decreased epithelial cell invasion and intracellular replication in epithelial cells and macrophages. The results suggest that quinolone-resistance may be associated with lower virulence and pathogenicity than in quinolone-susceptible strains.

  10. Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity.

    Science.gov (United States)

    Grande, Fedora; Aiello, Francesca; Garofalo, Antonio; Neamati, Nouri

    2016-01-01

    Design and discovery of new classes of anticancer agents with unique mechanisms of action is an urgent medical need. During the past several years, a series of salicylhydrazide class of compounds were reported to possess remarkable potency in a large panel of cancer cell lines from different tumor origins. In particular, the optimized lead compound, SC144, was further investigated and selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferative properties in various in vitro and in vivo xenograft models. This lead compound is active in cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an unique mechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinical development of SC144 will provide new therapeutic options for diverse cancers.

  11. Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.

    Science.gov (United States)

    Xie, Wenlin; Xie, Shimin; Zhou, Ying; Tang, Xufu; Liu, Jian; Yang, Wenqian; Qiu, Minghua

    2014-06-23

    A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed. PMID:24819956

  12. Anti-cancer agents based on N-acyl-2, 3-dihydro-1H-pyrrolo[2,3-b] quinoline derivatives and a method of making

    Science.gov (United States)

    Gakh, Andrei; Krasavin, Mikhail; Karapetian, Ruben; Rufanov, Konstantin A; Konstantinov, Igor; Godovykh, Elena; Soldatkina, Olga; Sosnov, Andrey V

    2013-04-16

    The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. In particular, the invention relates to N-acyl derivatives of 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines having the structural Formula (I), ##STR00001## stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. The meaning of R1 is independently selected from H; C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl substituents; R2 is selected from C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl; substituted or non-substituted, fused or non-fused to substituted or non-substituted aromatic ring, aryl or heteroaryl groups. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

  13. Anticancer agent-based marine natural products and related compounds.

    Science.gov (United States)

    Chen, Jian-Wei; Wu, Qi-Hao; Rowley, David C; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine natural products constitute a huge reservoir of anticancer agents. Consequently during the past decades, several marine anticancer compounds have been isolated, identified, and approved for anticancer treatment or are under trials. In this article the sources, structure, bioactivities, mode of actions, and analogs of some promising marine and derived anticancer compounds have been discussed. PMID:25559315

  14. Anticancer properties of lamellarins.

    Science.gov (United States)

    Bailly, Christian

    2015-03-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids. PMID:25706633

  15. Anticancer Properties of Lamellarins

    Directory of Open Access Journals (Sweden)

    Christian Bailly

    2015-02-01

    Full Text Available In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed here and the mechanistic portrait of lamellarin D is detailed. Lamellarins frequently serve as a starting point in the design of anticancer compounds. Extensive efforts have been devoted to create novel structures as well as to improve synthetic methods, leading to lamellarins and related pyrrole-derived marine alkaloids.

  16. Anticancer Properties of Lamellarins

    OpenAIRE

    Christian Bailly

    2015-01-01

    In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death. The pharmacology and chemistry of lamellarins are discussed ...

  17. Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria.

    OpenAIRE

    Chin, N X; Neu, H C

    1984-01-01

    The in vitro activity of ciprofloxacin, a quinolone-carboxylic acid derivative, was compared with those of norfloxacin, cefotaxime, cephalexin, ceftazidime, moxalactam, amoxicillin, and methicillin and other agents, as appropriate. The MICs of ciprofloxacin for 90% of members of the family Enterobacteriaceae and for Pseudomonas aeruginosa, Neisseria spp., and Bacteroides fragilis were between 0.005 and 0.8 micrograms/ml, whereas streptococci and staphylococci were all inhibited by less than o...

  18. DNA gyrase can cleave short DNA fragments in the presence of quinolone drugs.

    OpenAIRE

    Cove, M E; Tingey, A P; Maxwell, A

    1997-01-01

    We have analysed the DNA cleavage reaction of DNA gyrase using oligonucleotides annealed to a single-stranded M13 derivative containing a preferred gyrase cleavage site. We find that gyrase can cleave duplexes down to approximately 20 bp in size in the presence of the quinolone drugs ciprofloxacin and oxolinic acid. Ciprofloxacin shows a variation in its site specificity with an apparent preference for G bases adjacent to the cleavage sites, whereas oxolinic acid stimulates cleavage predomina...

  19. Transition-Metal-Free Cascade Synthesis of 4-Quinolones: Umpolung of Michael Acceptors via Ene Reaction with Arynes.

    Science.gov (United States)

    Santhosh Reddy, R; Lagishetti, Chandraiah; Kiran, I N Chaithanya; You, Hengyao; He, Yun

    2016-08-01

    A novel "one-pot" aryne transformation is described that affords various 4-quinolone derivatives without recourse to transition-metal catalysis. Arynes react with aza-Morita-Baylis-Hillman (AMBH) adducts through a cascade sequence involving an insertion/cyclization/ene reaction process to afford 4-quinolones in high yields with a broad substrate scope under mild reaction conditions. Essentially, an umpolung of reactivity at the β carbon of α,β-unsaturated ketone has been achieved by an inverse electron demand aryne-ene reaction to provide a C-arylated product. PMID:27434217

  20. On the mechanism of action of quinolone drugs.

    Science.gov (United States)

    Palumbo, M; Gatto, B; Zagotto, G; Palù, G

    1993-09-01

    Antibacterial quinolones are thought to inhibit DNA gyrase by trapping the enzyme as a complex with the DNA substrate. The precise molecular details of drug-DNA and drug-enzyme interactions remain controversial. Here, a model is proposed that accounts for the influence of magnesium ions on quinolone-DNA binding. PMID:8137121

  1. Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors

    DEFF Research Database (Denmark)

    Lager, Erik; Nilsson, Jakob; Nielsen, Elsebet Østergaard;

    2008-01-01

    The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABA(A) receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In...

  2. An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV and anti-cancer activities.

    Directory of Open Access Journals (Sweden)

    Ran He

    Full Text Available We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4 are significantly more potent in inhibiting human cytomegalovirus (CMV replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhibition and the slope parameter of dimers and monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy dimer (574, lacking the endoperoxide bridge, did not have any effect on CMV replication, suggesting a role for the endoperoxide bridge in CMV inhibition. Differences in anti-CMV activity were observed among three structural analogs of dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation state of the sulfur atom may contribute to its anti-CMV activity. Of all tested dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most potent inhibitor of CMV replication, with a selectivity index of approximately 1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active against a Ganciclovir-resistant CMV strain and was also the most active dimer in inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may represent a lead for development of a highly potent and safe anti-CMV compound.

  3. Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma.

    Science.gov (United States)

    Su, Jung-Chen; Chang, Jung-Hua; Huang, Jui-Wen; Chen, Peter P-Y; Chen, Kuen-Feng; Tseng, Ping-Hui; Shiau, Chung-Wai

    2015-02-25

    Obatoclax is an indole-pyrrole compound that induces cancer cell apoptosis through targeting the anti-apoptotic Bcl-2 protein family. Previously, we developed a series of obatoclax derivatives and studied their STAT3 inhibition-dependent activity against cancer cell lines. The obatoclax analog, prodigiosin, has been reported to mediate DNA cleavage in cancer cells by coordinating with copper complexes. To gain an understanding of copper-obatoclax complex activity, we applied obatoclax derivatives to examine their copper-mediated nuclease activity as a means to establish a basis for structure activity relationship. Replacement of the indole ring of obatoclax with furanyl, thiophenyl or Boc-indolyl rings reduced the DNA cleavage ability. The same effect was achieved through the replacement of the obatoclax pyrrolyl ring with thiazolidinedione and thioacetal. Among the compounds tested, we demonstrated that the complex of obatoclax or compound 7 with copper exhibited potent DNA strand scission which correlated with HCC cell growth inhibition.

  4. Synthesis, characterization and biological evaluation of N-ferrocenylmethyl amino acid benzene carboxamide derivatives and N-ferrocenyl benzoyl amino alkane derivatives as anti-cancer agents.

    OpenAIRE

    Butler, William E.

    2012-01-01

    The aim of this research was to explore the structure-activity relationship (SAR) of ferrocenyl-bioconjugates. A series of N-(ferrocenylmethylamino acid)-fluorinated-benzene carboxamide derivatives and a series of N-(ferrocenyl)-benzoyl-aminoalkane derivatives have been synthesised, structurally characterised and biologically evaluated for their anti-proliferative activity on various cancer cell lines, principally, the (estrogen receptor positive) MCF-7 breast cancer cell line. The anti-c...

  5. 2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: rational identification of a new anticancer lead.

    Science.gov (United States)

    Dutta Gupta, Sayan; Revathi, B; Mazaira, Gisela I; Galigniana, Mario D; Subrahmanyam, C V S; Gowrishankar, N L; Raghavendra, N M

    2015-04-01

    Hsp90 is a molecular chaperone that heals diverse array of biomolecules ranging from multiple oncogenic proteins to the ones responsible for development of resistance to chemotherapeutic agents. Moreover they are over-expressed in cancer cells as a complex with co-chaperones and under-expressed in normal cells as a single free entity. Hence inhibitors of Hsp90 will be more effective and selective in destroying cancer cells with minimum chances of acquiring resistance to them. In continuation of our goal to rationally develop effective small molecule azomethines against Hsp90, we designed few more compounds belonging to the class of 2,4-dihydroxy benzaldehyde derived imines (1-13) with our validated docking protocol. The molecules exhibiting good docking score were synthesized and their structures were confirmed by IR, (1)H NMR and mass spectral analysis. Subsequently, they were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The antiproliferative effect of the molecules were examined on PC3 prostate cancer cell lines by adopting 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. Finally, schiff base 13 emerged as the lead molecule for future design and development of Hsp90 inhibitors as anticancer agents.

  6. Synthesis and Anticancer Activity of Some Novel Tetralin-6-yl-pyrazoline, 2-Thioxopyrimidine, 2-Oxopyridine, 2-Thioxo-pyridine and 2-Iminopyridine Derivatives

    Directory of Open Access Journals (Sweden)

    Ebtehal S. Al-Abdullah

    2011-04-01

    Full Text Available The title compounds were prepared by reaction of 6-acetyltetralin (1 with different aromatic aldehydes 2a-c, namely 2,6-dichlorobenzaldehyde, 2,6-diflouro-benzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, to yield the corresponding a,b-unsaturated ketones 3a-c. Compound 3b was reacted with hydrazine hydrate to yield the corresponding 2-pyrazoline 4, while compounds 3a,b reacted with thiourea to afford the 2-thioxopyrimidine derivatives 5a,b, respectively. The reaction of 1, and the aromatic aldehydes 2a-c with ethyl cyanoacetate, 2-cyano-thioacetamide or malononitrile in the presence of ammonium acetate yielded the corresponding 2-oxopyridines 6a,b, 2-thioxopyridines 7a-c or 2-iminopyridines 8a,b, respectively. The newly prepared compounds were evaluated for anticancer activity against two human tumor cell lines. Compound 3a showed the highest potency with IC50 = 3.5 and 4.5 μg/mL against a cervix carcinoma cell line (Hela and breast carcinoma cell line (MCF7, respectively.

  7. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  8. Structure of PqsD, a Pseudomonas quinolone signal biosynthetic enzyme, in complex with anthranilate.

    Science.gov (United States)

    Bera, Asim K; Atanasova, Vesna; Robinson, Howard; Eisenstein, Edward; Coleman, James P; Pesci, Everett C; Parsons, James F

    2009-09-15

    Pseudomonas quinolone signal (PQS), 2-heptyl-3-hydroxy-4-quinolone, is an intercellular alkyl quinolone signaling molecule produced by the opportunistic pathogen Pseudomonas aeruginosa. Alkyl quinolone signaling is an atypical system that, in P. aeruginosa, controls the expression of numerous virulence factors. PQS is synthesized from the tryptophan pathway intermediate, anthranilate, which is derived either from the kynurenine pathway or from an alkyl quinolone specific anthranilate synthase encoded by phnAB. Anthranilate is converted to PQS by the enzymes encoded by the pqsABCDE operon and pqsH. PqsA forms an activated anthraniloyl-CoA thioester that shuttles anthranilate to the PqsD active site where it is transferred to Cys112 of PqsD. In the only biochemically characterized reaction, a condensation then occurs between anthraniloyl-PqsD and malonyl-CoA or malonyl-ACP, a second PqsD substrate, forming 2,4-dihydroxyquinoline (DHQ). The role PqsD plays in the biosynthesis of other alkyl quinolones, such as PQS, is unclear, though it has been reported to be required for their production. No evidence exists that DHQ is a PQS precursor, however. Here we present a structural and biophysical characterization of PqsD that includes several crystal structures of the enzyme, including that of the PqsD-anthranilate covalent intermediate and the inactive Cys112Ala active site mutant in complex with anthranilate. The structure reveals that PqsD is structurally similar to the FabH and chalcone synthase families of fatty acid and polyketide synthases. The crystallographic asymmetric unit contains a PqsD dimer. The PqsD monomer is composed of two nearly identical approximately 170-residue alphabetaalphabetaalpha domains. The structures show anthranilate-liganded Cys112 is positioned deep in the protein interior at the bottom of an approximately 15 A long channel while a second anthraniloyl-CoA molecule is waiting in the cleft leading to the protein surface. Cys112, His257, and

  9. Screening of quinolone antibiotic residues in beef sold in Kosovo

    Directory of Open Access Journals (Sweden)

    HAMDI ALIU

    2014-06-01

    Full Text Available This study aimed to find the effects of quinolone antibiotics in beef used in three regions of Kosovo. Total numbers of 89 beef meat samples were collected randomly from local meat shops for analysis. Extraction and determination of quinolones were made by ELISA procedure. Among the beef samples, 14 (15.7% of beef meat samples were positive for quinolones. The mean levels (±SE of quinolones were found to be in average of 28.22 ± 1.11 µg/kg in samples respectively for enrofloxacin, ciprofloxacin and flumequin. This study indicated that some beef meat sold in Kosovo contains residues of quinolone antibiotics. From the evaluation of tested samples is found positive the presence of enrofloxacin in 6 (6.7% beef meat samples and respectively for ciprofloxacin and fumequin in 3 (3, 35% and in 5(5, 6% beef meat samples. Study results confirmed quinolone residues in beef sold in Kosovo as constitute and serious risk for public health. Use of quinolones in treatment of cattle diseases in Kosovo remain an effective method of diseases control but are considered a common way of residues in beef produced and sold in Kosovo.

  10. Derivation of structure-activity relationships from the anticancer properties of ruthenium(II) arene complexes with 2-aryldiazole ligands.

    Science.gov (United States)

    Martínez-Alonso, Marta; Busto, Natalia; Jalón, Félix A; Manzano, Blanca R; Leal, José M; Rodríguez, Ana M; García, Begoña; Espino, Gustavo

    2014-10-20

    The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL)]Y [HL = HL(1), HL(2), or HL(3); Y = Cl or BF4; arene = 2-phenoxyethanol (phoxet), benzene (bz), or p-cymene (p-cym)]; (ii) dicationic aqua complexes of the formula [(η(6)-arene)Ru(OH2)(κ(2)-N,N-HL(1))](Y)2 (Y = Cl or TfO; arene = phoxet, bz, or p-cym); (iii) the nucleobase derivative [(η(6)-arene)Ru(9-MeG)(κ(2)-N,N-HL(1))](PF6)2 (9-MeG = 9-methylguanine); (iv) neutral complexes consistent with the formulation [(η(6)-arene)RuCl(κ(2)-N,N-L(1))] (arene = bz or p-cym); (v) the neutral cyclometalated complex [(η(6)-p-cym)RuCl(κ(2)-N,C-L(4))]. The cytototoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (MCR-5, MCF-7, A2780, and A2780cis) in order to establish structure-activity relationships. Three of the compounds with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL(1))]Cl differing in the arene moiety have been studied in depth in terms of thermodynamic dissociation constants, aquation kinetic constants, and DNA binding measurements. The biologically most active compound is the p-cym derivative, which strongly destabilizes the DNA double helix, whereas those with bz and phoxet have only a small effect on the stability of the DNA double helix. Moreover, the inhibitory activity of several compounds toward CDK1 has also been evaluated. The DNA binding ability of some of the studied compounds and their CDK1 inhibitory effect suggest a multitarget mechanism for their biological activity. PMID:25302401

  11. New Marine Derived Anticancer Therapeutics ─ A Journey from the Sea to Clinical Trials

    Directory of Open Access Journals (Sweden)

    J. Jimeno

    2004-02-01

    Full Text Available Abstract: Nature has been instrumental as a source for therapeutics. Despite the fact that we live in an oceanic planet, a number of technical factors have historically hampered the evolution of a marine-based chamanic medicine. With the implementation of scuba diving tools and the development of sophisticated instruments for the isolation and elucidation of structures of natural products from marine organisms, major advances have been made in the discovery of marine derived therapeutics. The availability of ARA-C, a nucleoside analog that is a basic component in the treatment of acute myeloid leukemia, and its fluorinated analog Gemcitabine, an important therapeutic tool in the treatment of pancreatic cancer and in non small cell lung cancer, is a solid proof and validation of the potential of this approach. As a result of our discovery and developmental program, three innovative compounds with novel mechanisms of action: ET-743, AplidinR and Kahalalide F, have been shown to display a positive therapeutic index and activity in resistant solid tumors that supports the ongoing clinical phase III/II trials. ET-743 represents the first active agent against sarcomas developed in the past 25 years and has demonstrated a therapeutic potential in pretreated ovarian cancer. Several chemical entities are under advanced preclinical testing and additional candidates for clinical development are emerging, including compounds hitting a specific target. Moreover, the development of a given marine candidate implies the collaboration of an interdisciplinary team special focused on supply, formulation, pharmacogenetics and preclinical toxicology.

  12. Synthesis and Characterization of Thiophene-derived Amido Bis-nitrogen Mustard and Its Antimicrobial and Anticancer Activities

    Institute of Scientific and Technical Information of China (English)

    唐一丹; 张景勍; 张少林; 耿蓉霞; 周成合

    2012-01-01

    The thiophene-derived amido bis-nitrogen mustard N2,N2,N5,N5-tetrakis(2-chloroethyl)-3,4-dimethylthio- phene-2,5-dicarboxamide was designed and synthesized via five-step reactions from commercially available 2-chloroacetonitrile. This target compound was confirmed by 1H NMR, 13C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X-ray single-crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug-resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC-3), breast carcinoma cell line (MCF-7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC-3) at a low dose. Keywords nitrogen mustard, thiophene, antibacterial, antifungal, cytotoxicity

  13. Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents

    Science.gov (United States)

    Helal, M. H.; El-Awdan, S. A.; Salem, M. A.; Abd-elaziz, T. A.; Moahamed, Y. A.; El-Sherif, A. A.; Mohamed, G. A. M.

    2015-01-01

    This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, 1H NMR, 13C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective.

  14. Synthesis, characterization and biological evaluation of anti-cancer indolizine derivatives via inhibiting β-catenin activity and activating p53.

    Science.gov (United States)

    Moon, Seong-Hee; Jung, Youngeun; Kim, Seong Hwan; Kim, Ikyon

    2016-01-01

    Diversity-oriented construction of new indolizine scaffolds was accomplished by utilizing domino Knoevenagel condensation/intramolecular aldol cyclization. Biological evaluation revealed anticancer activity of these compounds through inhibition of β-catenin and activation of p53. PMID:26608553

  15. Sesterterpenoids with Anticancer Activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2015-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  16. Synthesis, spectroscopic characterization and in vitro antimicrobial, anticancer and antileishmanial activities as well interaction with Salmon sperm DNA of newly synthesized carboxylic acid derivative, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid

    Science.gov (United States)

    Sirajuddin, Muhammad; Ali, Saqib; McKee, Vickie; Ullah, Hameed

    2015-03-01

    This paper stresses on the synthesis, characterization of novel carboxylic acid derivative and its application in pharmaceutics. Carboxylic acid derivatives have a growing importance in medicine, particularly in oncology. A novel carboxylic acid, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid, was synthesized and characterized by elemental analysis, FT-IR, NMR (1H, and 13C), mass spectrometry and single crystal X-ray structural analysis. The structure of the title compound, C11H12N2O6, shows the molecules dimerised by short intramolecular Osbnd H⋯O hydrogen bonds. The compound was screened for in vitro antimicrobial, anticancer, and antileishmanial activities as well as interaction with SS-DNA. The compound was also checked for in vitro anticancer activity against BHK-21, H-157 and HCEC cell lines, and showed significant anticancer activity. The compound was almost non-toxic towards human corneal epithelial cells (HCEC) and did not show more than 7.4% antiproliferative activity when used at the 2.0 μg/mL end concentration. It was also tested for antileishmanial activity against the promastigote form of leishmania major and obtained attractive result. DNA interaction study exposes that the binding mode of the compound with SS-DNA is an intercalative as it results in hypochromism along with minor red shift. A new and efficient strategy to identify pharmacophores sites in carboxylic acid derivative for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

  17. Increasing quinolone resistance in Salmonella enterica serotype enteritidis

    DEFF Research Database (Denmark)

    Mølbak, K.; Gerner-Smidt, P.; Wegener, Henrik Caspar

    2002-01-01

    Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use of...... quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use....

  18. 第三代喹喏酮类药物及其在淡水鱼类病害防治中的应用%Derivatives of fluorinated quinolones and their function in control of diseases of freshwater fish

    Institute of Scientific and Technical Information of China (English)

    刘艳辉; 张雅斌; 祖岫杰; 王拥军

    2001-01-01

    @@ 第三代喹诺酮类药物系70年代后期,80年代初期研制的一系列新型氟取代的喹诺酮类的衍生物(Derivatives of Fluorinated Qufinolones).该类药物已广泛应用于各种动物感染性疾病的预防和治疗,对大多数革兰氏阴性菌和部分革兰氏阳性菌及霉形体、衣原体、立克次氏体均有效.本类药物的开发应用,已引起世界各国的重视.在化学结构上其特点是喹啉环的6位上导入氟,而7位都连有哌嗪基的衍生物,使本来亲脂性良好的吡酮酸类(Pyridone Carboxylic Acid)药物,增加了适度的亲水性,降低了蛋白结合率,提高了生物利用率.抗菌谱较第一代、第二代喹诺酮类明显扩大,抗菌活性亦显著增强.

  19. CF3 Derivatives of the Anticancer Ru(III) Complexes KP1019, NKP-1339, and Their Imidazole and Pyridine Analogues Show Enhanced Lipophilicity, Albumin Interactions, and Cytotoxicity.

    Science.gov (United States)

    Chang, Stephanie W; Lewis, Andrew R; Prosser, Kathleen E; Thompson, John R; Gladkikh, Margarita; Bally, Marcel B; Warren, Jeffrey J; Walsby, Charles J

    2016-05-16

    The Ru(III) complexes indazolium [trans-RuCl4(1H-indazole)2] (KP1019) and sodium [trans-RuCl4(1H-indazole)2] (NKP-1339) are leading candidates for the next generation of metal-based chemotherapeutics. Trifluoromethyl derivatives of these compounds and their imidazole and pyridine analogues were synthesized to probe the effect of ligand lipophilicity on the pharmacological properties of these types of complexes. Addition of CF3 groups also provided a spectroscopic handle for (19)F NMR studies of ligand exchange processes and protein interactions. The lipophilicities of the CF3-functionalized compounds and their unsubstituted parent complexes were quantified by the shake-flask method to give the distribution coefficient D at pH 7.4 (log D7.4). The solution behavior of the CF3-functionalized complexes was characterized in phosphate-buffered saline (PBS) using (19)F NMR, electron paramagnetic resonance (EPR), and UV-vis spectroscopies. These techniques, along with fluorescence competition experiments, were also used to characterize interactions with human serum albumin (HSA). From these studies it was determined that increased lipophilicity correlates with reduced solubility in PBS but enhancement of noncoordinate interactions with hydrophobic domains of HSA. These protein interactions improve the solubility of the complexes and inhibit the formation of oligomeric species. EPR measurements also demonstrated the formation of HSA-coordinated species with longer incubation. (19)F NMR spectra show that the trifluoromethyl complexes release axial ligands in PBS and in the presence of HSA. In vitro testing showed that the most lipophilic complexes had the greatest cytotoxic activity. Addition of CF3 groups enhances the activity of the indazole complex against A549 nonsmall cell lung carcinoma cells. Furthermore, in the case of the pyridine complexes, the parent compound was inactive against the HT-29 human colon carcinoma cell line but showed strong cytotoxicity with CF3

  20. Stereoselective Synthesis and Anticancer Activities of New Podophyllotoxin Derivatives: 4-β -Cyano-4-Deoxy-4'-Demethylepipodophyllotoxin and 4-β -Carboxyl-4-Deoxy-4'-Demethylepipodophyllotoxin

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    4-β -Cyano-4-deoxy-4'-demethylepipodophyllotoxin 4 was synthesized from 4'-de -methylepipodophyllotoxin and Me3SiCN in the presence of BF3·Et2O. 4-β -Carboxyl-4-deoxy-4'-demethylepipodophyllotoxin 5 was obtained by hydrolyzing 4 in HOAc. Both of them show very high anticancer activities against L1210 and KB cell lines in vitro.

  1. Structure-based optimization and derivatization of 2-substituted quinolone-based non-nucleoside HCV NS5B inhibitors with submicromolar cellular replicon potency.

    Science.gov (United States)

    Cheng, Yu; Shen, Jian; Peng, Run-Ze; Wang, Gui-Feng; Zuo, Jian-Ping; Long, Ya-Qiu

    2016-06-15

    HCV NS5B polymerase is an attractive and validated target for anti-HCV therapy. Starting from our previously identified 2-aryl quinolones as novel non-nucleoside NS5B polymerase inhibitors, structure-based optimization furnished 2-alkyl-N-benzyl quinolones with improved antiviral potency by employing privileged fragment hybridization strategy. The N-(4-chlorobenzyl)-2-(methoxymethyl)quinolone derivative 5f proved to be the best compound of this series, exhibiting a selective sub-micromolar antiviral effect (EC50=0.4μM, SI=10.8) in Huh7.5.1 cells carrying a HCV genotype 2a. Considering the undesirable pharmacokinetic property of the highly substituted quinolones, a novel chemotype of 1,6-naphthyridine-4,5-diones were evolved via scaffold hopping, affording brand new structure HCV inhibitors with compound 6h (EC50 (gt2a)=2.5μM, SI=7.2) as a promising hit. Molecular modeling studies suggest that both of 2-alkyl quinolones and 1,6-naphthyridine-4,5-diones function as HCV NS5B thumb pocket II inhibitors. PMID:27133482

  2. Synthesis and structure-activity relationship of N-(2-arylethyl) isoquinoline derivatives as anti-cancer agents%N-芳乙基异喹啉衍生物的合成及其抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    汪燕翔; 赵午莉; 毕重文; 李阳彪; 邵荣光; 宋丹青

    2012-01-01

    A series of novel N-(2-arylethyl) isoquinoline derivatives were designed, synthesized and evaluated for their anti-cancer activities. Among these analogs, compound 9a exhibited the potential anti-cancer activities on HepG2 and HCT116 cells with IC50 values of 2.52 and 1.99 μg·mL-1, respectively. Cell cycle was blocked at S phase of HepG2 cells treated with 9a by flow cytometry detection. Our results provided a basis for the development of a new series of anti-cancer candidates.%本研究采用一种简便的新方法设计合成了一系列全新结构的N-芳乙基异喹啉衍生物,并对其体外抗肿瘤活性进行了评价.其中化合物9a表现出较强的抗肿瘤活性,对人肝癌HepG2和大肠癌HCT116细胞的IC50值分别为2.52和1.99 μg·mL-1.初步作用机制显示,9a可以将HepG2细胞周期阻滞于S期,使细胞增殖受阻,达到抗肿瘤效果.

  3. 1,10-菲咯啉及其衍生物铜配合物的抗癌活性研究进展%Progress of Anticancer Activities of Copper Complexes with1,10-Phenanthroline and its Derivatives

    Institute of Scientific and Technical Information of China (English)

    夏寺丰; 鲁晓明

    2011-01-01

    As bio-essential trace element,copper plays an important role in biological processes,and many copper complexes have the activity of anti-proliferation of cancer cells.The progress in anti-cancer activity of copper complexes with 1,10-phenanthroline and its derivatives was reviewed,and the proposal mechanism of oxidative cleavage of DNA by different sorts of copper complexes was discussed.In addition,the prospects of copper complexes as anti-cancer drugs were presented by comparison with cisplatin anti-cancer drugs.%作为一种微量生命元素,铜在生物进程中扮演着重要角色,很多铜配合物呈现抑制癌细胞增殖的活性。本文论述了以1,10-菲咯啉及其衍生物为配体的铜配合物的抗癌活性研究进展,分析了其对DNA裂解的可能机理。对比顺铂类抗癌药物,展望了铜配合物作为抗癌药物的应用前景。

  4. Novel anticancer agents from plant sources

    Institute of Scientific and Technical Information of China (English)

    Shah Unnati; Shah Ripal; Acharya Sanjeev; Acharya Niyati

    2013-01-01

    Plants remain an important source of new drugs,new drug leads and new chemical entities.Plant based drug discovery resulted mainly in the development of anticancer and anti-infectious agents,and continues to contribute to the new leads in clinical trials.Natural product drugs play a dominant role in pharmaceutical care.Several plant-derived compounds are currently successfully employed in cancer treatment.There are many classes of plant-derived cytotoxic natural products studied for further improvement and development of drugs.New anticancer drugs derived from research on plant antitumor agents will be continuously discovered.The basic aim of this review is to explore the potential of newly discovered anticancer compounds from medicinal plants,as a lead for anticancer drug development.It will be helpful to explore the medicinal value of plants and for new drug discovery from them for the researchers and scientists around the globe.

  5. Quinolone Resistance Mechanisms Among Salmonella enterica in Malaysia.

    Science.gov (United States)

    Thong, Kwai Lin; Ngoi, Soo Tein; Chai, Lay Ching; Teh, Cindy Shuan Ju

    2016-06-01

    The prevalence of quinolone-resistant Salmonella enterica is on the rise worldwide. Salmonella enterica is one of the major foodborne pathogens in Malaysia. Therefore, we aim to investigate the occurrence and mechanisms of quinolone resistance among Salmonella strains isolated in Malaysia. A total of 283 Salmonella strains isolated from food, humans, and animals were studied. The disk diffusion method was used to examine the quinolone susceptibility of the strains, and the minimum inhibitory concentration (MIC) values of nalidixic acid and ciprofloxacin were also determined. DNA sequencing of the quinolone resistance-determining regions (QRDRs) of gyrase and topoisomerase IV genes and the plasmid-borne qnr genes was performed. The transfer of the qnr gene was examined through transconjugation experiment. A total of 101 nalidixic acid-resistant Salmonella strains were identified. In general, all strains were highly resistant to nalidixic acid (average MICNAL, 170 μg/ml). Resistance to ciprofloxacin was observed in 30.7% of the strains (1 ≤ MICCIP ≤ 2 μg/ml). Majority of the strains contained missense mutations in the QRDR of gyrA (69.3%). Silent mutations were frequently detected in gyrB (75.2%), parC (27.7%), and parE (51.5%) within and beyond the QRDRs. Novel mutations were detected in parC and parE. The plasmid-borne qnrS1 variant was found in 36.6% of the strains, and two strains were found to be able to transfer the qnrS1 gene. Overall, mutations in gyrA and the presence of qnrS1 genes might have contributed to the high level of quinolone resistance among the strains. Our study provided a better understanding on the status of quinolone resistance among Salmonella strains circulating in Malaysia. PMID:26683630

  6. Crude extracts of marine-derived and soil fungi of the genus Neosartorya exhibit selective anticancer activity by inducing cell death in colon, breast and skin cancer cell lines

    Directory of Open Access Journals (Sweden)

    Alice Abreu Ramos

    2016-01-01

    Full Text Available Background: The crude ethyl acetate extracts of marine-derived fungi Neosartorya tsunodae KUFC 9213 (E1 and N. laciniosa KUFC 7896 (E2, and soil fungus N. fischeri KUFC 6344 (E3 were evaluated for their in vitro anticancer activities on a panel of seven human cancer cell lines. Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was performed, after 48 h treatments with different concentrations of extracts, to determine their concentration of the extract or Dox that inhibits cell viability by 50% for each cell line. The effects of the crude extracts on DNA damage, clonogenic potential and their ability to induce cell death were also assessed. Results: E1 was found to the void of anti-proliferative effects. E2 was shown to decrease the clonogenic potential in human colorectal carcinoma cell line (HCT116, human malignant melanoma cell line (A375, human breast adenocarcinoma cell line (MCF7, and human caucasian colon adenocarcinoma Grade II cell line (HT29 cells, whereas E3 showed such effect only in HCT116 and MCF7 cells. Both extracts were found to increase DNA damage in some cell lines. E2 was found to induce cell death in HT29, HCT116, MCF7, and A375 cells while extract E3 increased cell death in MCF7 and HCT116 cell lines. Conclusion: The results reveal that E2 and E3 possess anticancer activities in human colon carcinoma, breast adenocarcinoma, and melanoma cells, validating the interest for an identification of molecular targets involved in the anticancer activity.

  7. Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer.

    Science.gov (United States)

    Dexheimer, Thomas S; Rosenthal, Andrew S; Luci, Diane K; Liang, Qin; Villamil, Mark A; Chen, Junjun; Sun, Hongmao; Kerns, Edward H; Simeonov, Anton; Jadhav, Ajit; Zhuang, Zhihao; Maloney, David J

    2014-10-01

    Deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases including cancer. The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1), in association with UAF1 (USP1-associated factor 1), is a known regulator of DNA damage response and has been shown as a promising anticancer target. To further evaluate USP1/UAF1 as a therapeutic target, we conducted a quantitative high throughput screen of >400000 compounds and subsequent medicinal chemistry optimization of small molecules that inhibit the deubiquitinating activity of USP1/UAF1. Ultimately, these efforts led to the identification of ML323 (70) and related N-benzyl-2-phenylpyrimidin-4-amine derivatives, which possess nanomolar USP1/UAF1 inhibitory potency. Moreover, we demonstrate a strong correlation between compound IC50 values for USP1/UAF1 inhibition and activity in nonsmall cell lung cancer cells, specifically increased monoubiquitinated PCNA (Ub-PCNA) levels and decreased cell survival. Our results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as a molecular target for anticancer therapies. PMID:25229643

  8. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  9. Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

    Directory of Open Access Journals (Sweden)

    Mehul M. Patel

    2014-01-01

    Full Text Available Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl-2-(substituted-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT by Schrodinger’s Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections.

  10. Synthesis of Novel 1-Substituted and 1,9-Disubstituted-1,2,3,4-tetrahydro-9H-Carbazole Derivatives as Potential Anticancer Agents

    Directory of Open Access Journals (Sweden)

    H. I. El-Diwani

    2000-10-01

    Full Text Available Condensation of 1-acetyl-1,2,3,4-tetrahydro-9H-carbazole (2 with some amino compounds furnished the corresponding imino derivatives 3a-e. Compound 3a reacted with chloroacetic acid and underwent cyclization to give the thiazolidine derivative 5. Also, treatment of 3c with thionyl chloride caused cyclization to yield the [1,2,6]thiadiazino derivative 6, which gave the corresponding N-formyl derivative 7 upon heating with ethyl formate. In addition, interaction of 3d with ethyl cyanoacetate yielded the monoamide of malonic acid derivative 8. Acylation of carbazole 1 with succinoyl chloride or phenylacetyl choride produced the corresponding azepine (11 and 1,9-diphenyl acetyl derivatives (14, respectively. Compounds 11, 14 were further reacted to give the carbazole derivatives 12, 13 and 15a,b. The cytotoxic activity for some of the prepared compounds against breast cancer B20 is discussed.

  11. Resistance to quinolones in Campylobacter jejuni and Campylobacter coli from Danish broilers at farm level

    DEFF Research Database (Denmark)

    Pedersen, Karl; Wedderkopp, A.

    2003-01-01

    Aims : To investigate the prevalence of quinolone resistance among Campylobacter jejuni and Camp. coli isolates from Danish poultry at the farm level, as well as for the whole country. Methods and Results : Data and isolates were collected from a national surveillance of Campylobacter in poultry....... Quinolone resistance was investigated by determination of minimum inhibitory concentration (MIC) to nalidixic acid and enrofloxacin. Among Camp. jejuni and Camp. coli combined, 7.5% were resistant to nalidixic acid. Quinolone resistance varied considerably from farm to farm, with 0% on some farms and almost...... 100% on others, but the resistance was evenly distributed geographically. With respect to isolates from farms where resistance was detected, quinolone resistance was higher among Camp. coli (28.7%) than among Camp. jejuni (11.3%). PFGE typing of quinolone-resistant and quinolone-susceptible isolates...

  12. 2H-1-苯并吡喃衍生物的合成及其体外抗癌活性的初步评价%Synthesis and initially anticancer activity evaluation of novel 2 H-1-benzopyran derivatives

    Institute of Scientific and Technical Information of China (English)

    聂爱华; 顾为; 王勇俊; 黄子为

    2008-01-01

    Aim To design and synthesize novel 2H-1-benzopyran derivatives and to evaluate their anticancer activity.Methods 2'-Hydroxychalcones were transferred to flavones derivatives under microwave irradiation.The flavones derivatives were reacted with POCl3 to get 4-chloro-2H-chromene-3-carbaldehydes.Novel 2H-1-benzopyran derivatives were prepared by the reaction of various 4-chloro-2H-chromene-3-carbaldehydes with R3CONHNH2 under microwave irradiation combining solution phase parallel synthesis.HL-60 cell line was employed to evaluate anticancer activity of these compounds in vitro.Results and conclusion A combinatorial library containing 32 novel 2H-1-benzopyran derivatives was synthesized.Some of these compounds exhibited inhibitory activity against HL-60 cell proliferation.The inhibitory rate of compound 9e was 70.8% at the concentration of 30 μmol·L-1.%目的 设计并合成2H-1-苯并吡喃衍生物化合库并对其体外抗癌活性进行评价.方法 以2'-羟基查耳酮为原料通过微波促进合成得到黄酮衍生物中间体,此中间体与POC13反应得到4-氯-2H-色原烯-3-醛,通过微波辅助液相平行合成的方法.此醛与R3CONHNH2反应得到2H-1-苯并吡喃衍生物化合库.利用HL-60细胞系评价该化合物库的体外抗癌活性.结果 与结论合成了含有32个化合物的2H-1-苯并吡喃衍生物库,体外活性评价表明,部分化合物对HL-60细胞的增殖有一定的抑制作用,其中,化合物9e在浓度为30μmol·L-1的抑制率为70.8%.

  13. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin

    OpenAIRE

    Kocsis, Bela; Domokos, J.; Szabo, D.

    2016-01-01

    Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their...

  14. The Emergence of Quinolone Resistant Shigella sonnei, Pondicherry, India.

    Science.gov (United States)

    Das, Ankita; Natarajan, Mailan; Mandal, Jharna

    2016-01-01

    Ciprofloxacin resistant Shigella sonnei across the globe have been increasing alarmingly. In order to understand the emergence of S.sonnei with respect to ciprofloxacin resistance in our patient population, the following study was carried out. Of the 184 Shigella sp. Isolated from 2012 to 2015, 34 S.sonnei which were confirmed by standard methods and subjected to antimicrobial susceptibility testing were selected. The minimum inhibitory concentrations (MICs) of 16/34 quinolone resistant isolates tested ranged from 4micrograms/ml to 16micrograms/ml for ciprofloxacin, from 16 micrograms/ml to 64 micrograms/ml for ofloxacin and from 16micrograms/ml to 64micrograms/ml for levofloxacin. Sequence determination of the quinolone resistance determining regions of gyrA, gyrB, parC, and parE genes showed mutations in GyrA at Gln69/Trp, Phe71/Ser, Ser72/Pro, Met75/Leu, Ser90/Cys, Met94/Leu, His106/Pro, Asn161/His, Thr163/Ala and in ParC at Ala64/Asp. Among the plasmid-mediated quinolone resistance (PMQRs) targets investigated,qnrB was the most (93.7%) prevalent followed by qnrC (18.7%). None hadqnrA, qnrS and qepA. Two (0.1%) of the isolates harboured theaac(6')-lb gene. Drug accumulation assay detected the presence of efflux pump activity in 9/15 (60%) among ciprofloxacin resistant isolates. All isolates harboured the ipaH gene followed by ial (17.6%), sen (11.7%), set1A&set1B (5.8%) genes. None had stx1 element. PCR for Enterobacterial repetitive intergenic consensus (ERIC) sequences resulted in 4 unique clusters, of which Type III was the most (44%) dominant but there was no correlation between the ERIC types and the antibiotic resistance pattern or the virulence profile. A documented increase in S.sonnei harbouring the qnrgenes and some unusual genes like set1Aand indicate an ongoing process of horizontal gene transfer. The accumulation of novel mutations in GyrA and ParC in the presence of efflux pump and PMQR genes contributed to the raised MIC to quinolones. These

  15. Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations in quinolone-resistant Escherichia coli isolated from humans and swine in Denmark

    DEFF Research Database (Denmark)

    Cavaco, Lina; Frimodt-Møller, Niels; Hasman, Henrik;

    2008-01-01

    Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were investigated in 124 Escherichia coli isolated from humans (n = 85) and swine (n = 39) in Denmark. The collection included 59 high-level CIP......-resistant isolates (MIC >= 4) from human (n = 51) and pig origin (n = 8) and 65 low-level CIP-resistant isolates (MIC >= 0.125) from human (n = 34) and pig origin (n = 31). Resistance by target modification was screened by PCR amplification and sequencing, of the quinolone resistance determining regions (QRDRs) of......A and qnrS genes conferring quinolone resistance by target protection were detected in two human low-level CIP-resistant isolates that did not display NAL resistance. As expected, target mutation in QRDRs was the most prevalent mechanism of quinolone resistance. This mechanism was complemented by efflux...

  16. Quinolone-1-(2H)-ones as hedgehog signalling pathway inhibitors.

    Science.gov (United States)

    Trinh, Trieu N; McLaughlin, Eileen A; Abdel-Hamid, Mohammed K; Gordon, Christopher P; Bernstein, Ilana R; Pye, Victoria; Cossar, Peter; Sakoff, Jennette A; McCluskey, Adam

    2016-07-14

    A series of quinolone-2-(1H)-ones derived from the Ugi-Knoevenagel three- and four-component reaction were prepared exhibiting low micromolar cytotoxicity against a panel of eight human cancer cell lines known to possess the Hedgehog Signalling Pathway (HSP) components, as well as the seminoma TCAM-2 cell line. A focused SAR study was conducted and revealed core characteristics of the quinolone-2-(1H)-ones required for cytotoxicity. These requirements included a C3-tethered indole moiety, an indole C5-methyl moiety, an aliphatic tail or an ester, as well as an additional aromatic moiety. Further investigation in the SAG-activated Shh-LIGHT2 cell line with the most active analogues: 2-(3-cyano-2-oxo-4-phenylquinolin-1(2H)-yl)-2-(1-methyl-1H-indol-3-yl)-N-(pentan-2-yl)acetamide (5), 2-(3-cyano-2-oxo-4-phenylquinolin-1(2H)-yl)-2-(5-methyl-1H-indol-3-yl)-N-(pentan-2-yl)acetamide (23) and ethyl (2-(3-cyano-2-oxo-4-phenylquinolin-1(2H)-yl)-2-(5-methyl-1H-indol-3-yl)acetyl)glycinate (24) demonstrated a down regulation of the HSP via a reduction in Gli expression, and in the mRNA levels of Ptch1 and Gli2. Analogues 5, 23 and 24 returned in cell inhibition values of 11.6, 2.9 and 3.1 μM, respectively, making this new HSP-inhibitor pharmacophore amongst the most potent non-Smo targeted inhibitors thus far reported. PMID:27272335

  17. Pharmacokinetics: metabolism and renal excretion of quinolones in man.

    Science.gov (United States)

    Vree, T B; Wijnands, W J; Guelen, P J; Baars, A M; Hekster, Y A

    1986-02-21

    The quinolones are relatively poorly absorbed from the gastrointestinal tract. The elimination proceeds mainly by renal excretion. The half-life of elimination depends on the molecular structure and varies between 2 and 10 h. Impaired kidney function is expected to increase the half-life of elimination, though this effect is not always observed. Since the 4-oxo-metabolites show a higher renal clearance than the parent drug, renal impairment will result in a cumulation of the metabolites in the body. PMID:3960691

  18. Continuous-flow microreactor multi-step synthesis of an aminonaphthalene derivative as starting material for the preparation of novel anticancer agents

    OpenAIRE

    Tietze, Lutz F.; Liu, Deshan

    2008-01-01

    A multi-step synthesis of the aminonaphthalene derivate 1 as a key intermediate in the synthesis of the duocarmycin based prodrug 2 for a selective treatment of cancer in a microreactor is described. The conditions for the synthesis in the batch mode were adjusted for application in a microreactor and the results of both methods were compared showing that the transformations in the microreactor in most cases give similar or even better results with the advantage of a continuous...

  19. Genome-based Characterization of Two Prenylation Steps in the Assembly of the Stephacidin and Notoamide Anticancer Agents in a Marine-derived Aspergillus sp

    OpenAIRE

    Ding, Yousong; de Wet, Jeffrey R.; Cavalcoli, James; Li, Shengying; Greshock, Thomas J.; Miller, Kenneth A.; Finefield, Jennifer M.; Sunderhaus, James D.; McAfoos, Timothy; Tsukamoto, Sachiko; Williams, Robert M.; Sherman, David H.

    2010-01-01

    Stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing a core bicyclo[2.2.2]diazaoctane ring system. These bioactive fungal secondary metabolites have a range of unusual structural and stereochemical features but their biosynthesis has remained uncharacterized. Herein, we report the first biosynthetic gene cluster for this class of fungal alkaloids based on whole genome sequencing of a marine-derived Aspergillus sp. Two central pathway enzymes c...

  20. SKLB-163, a new benzothiazole-2-thiol derivative, exhibits potent anticancer activity by affecting RhoGDI/JNK-1 signaling pathway

    OpenAIRE

    Peng, X; Xie, G; Z. Wang; H. Lin; Zhou, T.; Xiang, P.; Jiang, Y.(Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China; Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui, China; Department of Physics, Nanjing University, Nanjing, Jiangsu, China; School of Physics, Shandong University, Jinan, Shandong, China; Physics Department, Shanghai Jiao Tong University, Shanghai, China); Yang, S.; Wei, Y.; Yu, L.; Zhao, Y.

    2014-01-01

    Small-molecule inhibitors are an attractive therapeutic approach for most types of human cancers. SKLB-163, a novel benzothiazole-2-thiol derivative, was developed via computer-aided drug design and de novo synthesis. MTT assay showed it had potent anti-proliferative activity on various human cancer cells. Treatment of cancer cells with SKLB-163 induced obvious apoptosis and inhibited proliferation in vitro. SKLB-163 administered p.o. showed a marked antitumor activity in vivo. Proteomic tech...

  1. Computer Based Design and Synthesis of Some Novel Thiazole Derivatives Bearing a Sulfonamide Moiety and Studying Their Potential Synergistic Anticancer Effect With γ-Irradiation

    International Nuclear Information System (INIS)

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new thiazole, thiazolo pyrimidine, thiazolo pyrane and thiazolo pyrano pyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  2. Synthesis and in vitro cytotoxicity of novel C-12 substituted-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

    Science.gov (United States)

    Kandanur, Sai Giridhar Sarma; Golakoti, Nageswara Rao; Nanduri, Srinivas

    2015-12-15

    Andrographolide, the major labdane diterpenoid from Andrographis paniculata has been reported to be cytotoxic against various cancer cells in vitro. Our research efforts led to the discovery of novel 12-phenyl thio and 12-aryl amino-14-deoxy-andrographolide derivatives (III q and III r) with potent cytotoxic activity, 12-benzyl amino-14-deoxy-andrographolide analogues showing broad range of cytotoxic activity against most of the cell lines and 12-alkyl amino-14-deoxy-andrographolide derivatives being selective to few cell lines (PC-3 and HOP-92), when the selected analogues were evaluated against 60 human cancer cell line panel at National Cancer Institute (N.C.I.), USA. The SAR (structure activity relationship) studies demonstrated potent activity for the compounds containing the following functionalities at C-12: substituted aryl amino/phenyl thio>benzylamine>alkyl amine. The significant cytotoxic activity observed for compounds III q and III r suggest that these could serve as templates for further optimization. PMID:26561364

  3. New water-soluble ruthenium(II) terpyridine complexes for anticancer activity: synthesis, characterization, activation kinetics, and interaction with guanine derivatives.

    Science.gov (United States)

    Rilak, Ana; Bratsos, Ioannis; Zangrando, Ennio; Kljun, Jakob; Turel, Iztok; Bugarčić, Živadin D; Alessio, Enzo

    2014-06-16

    With the aim of assessing whether ruthenium(II) compounds with meridional geometry might be utilized as potential antitumor agents, a series of new, water-soluble, monofunctional ruthenium(II) complexes of the general formula mer-[Ru(L3)(N-N)X][Y]n (where L3 = 2,2':6',2″-terpyridine (tpy) or 4'-chloro-2,2':6',2″-terpyridine (Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach), or 2,2'-bipyridine (bpy); X = Cl or dmso-S; Y = Cl, PF6, or CF3SO3; n = 1 or 2, depending on the nature of X) were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them, i.e., [Ru(Cl-tpy)(bpy)Cl][Cl] (3Cl), [Ru(Cl-tpy)(en)(dmso-S)][Y]2 [Y = PF6 (6PF6), CF3SO3 (6OTf)] and [Ru(Cl-tpy)(bpy)(dmso-S)][CF3SO3]2 (8OTf), the X-ray structure was also determined. The new terpyridine complexes, with the exception of 8, are well soluble in water (>25 mg/mL). (1)H and (31)P NMR spectroscopy studies performed on the three selected complexes [Ru(Cl-tpy)(N-N)Cl](+) [N-N = en (1), dach (2), and bpy (3)] demonstrated that, after hydrolysis of the Cl ligand, they are capable of interacting with guanine derivatives [i.e., 9-methylguanine (9MeG) or guanosine-5'-monophosphate (5'-GMP)] through N7, forming monofunctional adducts with rates and extents that depend strongly on the nature of N-N: 1 ≈ 2 ≫ 3. In addition, compound 1 shows high selectivity toward 5'-GMP compared to adenosine-5'-monophosphate (5'-AMP), in a competition experiment. Quantitative kinetic investigations on 1 and 2 were performed by means of UV/visible spectroscopy. Overall, the complexes with bidentate aliphatic diamines proved to be superior to those with bpy in terms of solubility and reactivity (i.e., release of Cl(-) and capability to bind guanine derivatives). Contrary to the chlorido compounds, the corresponding dmso derivatives proved to be inert (viz., they do not release the monodentate ligand) in

  4. Anti-cancer effects of 2-oxoquinoline derivatives on the HCT116 and LoVo human colon cancer cell lines.

    Science.gov (United States)

    Fang, Feng-Qi; Guo, Hui-Shu; Zhang, Jie; Ban, Li-Ying; Liu, Ji-Wei; Yu, Pei-Yao

    2015-12-01

    The present study demonstrated the anti-tumor effects of the quinoline derivative [5-(3-chloro-oxo-4-phenyl-cyclobutyl)-quinoli-8-yl-oxy] acetic acid hydrazide (CQAH) against colorectal carcinoma. Substantial apoptotic effects of CQAH on HCT116 and LoVo human colon cancer cell lines were observed. Apoptosis was identified based on cell morphological characteristics, including cell shrinkage and chromatin condensation as well as Annexin V/propidium iodide double staining followed by flow cytometric analysis and detection of apoptosis-associated proteins by western blot analysis. CQAH induced caspase-3 and PARP cleavage, reduced the expression of the anti-apoptotic proteins myeloid cell leukemia-1 and B-cell lymphoma (Bcl) extra large protein and elevated the expression of the pro-apoptotic protein Bcl-2 homologous antagonist killer. In addition, pharmacological inhibition of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, significantly reduced CQAH-mediated cell death as well as cleavage of caspase-3 and PARP. Co-treatment of CQAH with the commercial chemotherapeutics 5-fluorouracil and camptothecin-11 significantly improved their efficacies. Comparison of the apoptotic effects of CQAH with those of two illustrated structure-activity associations for this compound type, indicating that substitution at position-4 of the azetidine phenyl ring is pivotal for inducing apoptosis. In conclusion, the results of the present study indicated CQAH and its analogues are potent candidate drugs for the treatment of colon carcinoma.

  5. Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01: targeting vascular endothelial growth factor receptor signaling and angiogenesis.

    Science.gov (United States)

    Yang, Hung-Yu; Hsu, Ya-Fen; Chiu, Pei-Ting; Ho, Shiau-Jing; Wang, Chi-Han; Chi, Chih-Chin; Huang, Yu-Han; Lee, Cheng-Feng; Li, Ying-Shiuan; Ou, George; Hsu, Ming-Jen

    2013-01-01

    Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.) Cuss., was recently shown to enhance learning and memory in rats. In this study, we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX) in an effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and endothelial tube formation in human umbilical endothelial cells (HUVECs). BMX also attenuated VEGF-induced microvessel sprouting from aortic rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. Taken together, this study provides evidence that BMX modulates vascular endothelial cell remodeling and leads to the inhibition of tumor angiogenesis. These results also support the role of BMX as a potential drug candidate and warrant the clinical development in the treatment of cancer. PMID:24312323

  6. An Efficient Synthesis of 1-Alkyl-2-phenyl-4-quinolones from 2-Halobenzoic Acids

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yoon Ju; Choi, Jin Sun; Lee, Jae In [Duksung Women' s Univ., Seoul (Korea, Republic of)

    2013-10-15

    The present method offers an efficient synthesis of 1-alkyl-2-phenyl-4-quinolones from 2-haloben-zoic acids. It has the advantages with respect to (i) synthesis of 2 equiv of alkynones 5 from 1 equiv of 4,6-pyrimidyl di(2-halobenzoates) 3, (ii) synthesis of versatile 1-alkyl-2-phenyl-4-quinolones in high overall yields, and (iii) use of readily available and cheap starting materials. Therefore, this method could be utilized as a practical synthesis of 1-alkyl-2-phenyl-4-quinolones. Several methods have been developed to synthesize 1-alkyl-2-phenyl-4-quinolones from 2'-substituted acetophenones, anilines, and 2-halobenzoyl chlorides as starting materials. The reaction of N-methylisatoic anhydride with the lithium enolate of an 4'-methoxyacetophenone afforded the 1-methyl-2-phenyl-4-quinolone in a short sequence, but the yield was low. N-(2-Acetylphenyl)benzamides, prepared by Friedel-Crafts acylation of N-phenyl benzamides with acetyl chloride or benzoylation of 2'-aminoacetophenones with benzoyl chlorides,8 were cyclized with potassium t-butoxide to yield 2-aryl-4-quinolones, which were further alkylated with alkyl iodides to give 1-alkyl-2-aryl-4-quinolones.

  7. Diospyrin derivative, an anticancer quinonoid, regulates apoptosis at endoplasmic reticulum as well as mitochondria by modulating cytosolic calcium in human breast carcinoma cells

    International Nuclear Information System (INIS)

    Highlights: ► Diospyrin diethylether (D7) caused oxidative stress-dependent activation of PC-PLC. ► Activated PC-PLC induced a sustained-release of Ca2+ from endoplasmic reticulum. ► The elevated cytosolic Ca+2 led to the calpain-caspase12 dependent apoptosis. ► D7-Induced Ca+2 also found to accentuate the mitochondrial pathway of apoptosis. -- Abstract: Diospyrin diethylether (D7), a bisnaphthoquinonoid derivative, exhibited an oxidative stress-dependent apoptosis in several human cancer cells and tumor models. The present study was aimed at evaluation of the increase in cytosolic calcium [Ca2+]c leading to the apoptotic cell death triggered by D7 in MCF7 human breast carcinoma cells. A phosphotidylcholine-specific phospholipase C (PC-PLC) inhibitor, viz. U73122, and an antioxidant, viz. N-acetylcysteine, could significantly prevent the D7-induced rise in [Ca2+]c and PC-PLC activity. Using an endoplasmic reticulum (ER)-Ca2+ mobilizer (thapsigargin) and an ER-IP3R antagonist (heparin), results revealed ER as a major source of [Ca2+]c which led to the activation of calpain and caspase12, and cleavage of fodrin. These effects including apoptosis were significantly inhibited by the pretreatment of Bapta-AM (a cell permeable Ca2+-specific chelator), or calpeptin (a calpain inhibitor). Furthermore, D7-induced [Ca2+]c was found to alter mitochondrial membrane potential and induce cytochrome c release, which was inhibited by either Bapta-AM or ruthenium red (an inhibitor of mitochondrial Ca2+ uniporter). Thus, these results provided a deeper insight into the D7-induced redox signaling which eventually integrated the calcium-dependent calpain/caspase12 activation and mitochondrial alterations to accentuate the induction of apoptotic cell death.

  8. Diospyrin derivative, an anticancer quinonoid, regulates apoptosis at endoplasmic reticulum as well as mitochondria by modulating cytosolic calcium in human breast carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Binod [Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032 (India); Radiation and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kumar, Amit [Radiation and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Ghosh, Subhalakshmi [Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032 (India); Pandey, Badri N., E-mail: bnp@barc.gov.in [Radiation and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Mishra, Kaushala P. [Radiation and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Hazra, Banasri, E-mail: banasrihazra@yahoo.co.in [Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032 (India)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Diospyrin diethylether (D7) caused oxidative stress-dependent activation of PC-PLC. Black-Right-Pointing-Pointer Activated PC-PLC induced a sustained-release of Ca{sup 2+} from endoplasmic reticulum. Black-Right-Pointing-Pointer The elevated cytosolic Ca{sup +2} led to the calpain-caspase12 dependent apoptosis. Black-Right-Pointing-Pointer D7-Induced Ca{sup +2} also found to accentuate the mitochondrial pathway of apoptosis. -- Abstract: Diospyrin diethylether (D7), a bisnaphthoquinonoid derivative, exhibited an oxidative stress-dependent apoptosis in several human cancer cells and tumor models. The present study was aimed at evaluation of the increase in cytosolic calcium [Ca{sup 2+}]{sub c} leading to the apoptotic cell death triggered by D7 in MCF7 human breast carcinoma cells. A phosphotidylcholine-specific phospholipase C (PC-PLC) inhibitor, viz. U73122, and an antioxidant, viz. N-acetylcysteine, could significantly prevent the D7-induced rise in [Ca{sup 2+}]{sub c} and PC-PLC activity. Using an endoplasmic reticulum (ER)-Ca{sup 2+} mobilizer (thapsigargin) and an ER-IP3R antagonist (heparin), results revealed ER as a major source of [Ca{sup 2+}]{sub c} which led to the activation of calpain and caspase12, and cleavage of fodrin. These effects including apoptosis were significantly inhibited by the pretreatment of Bapta-AM (a cell permeable Ca{sup 2+}-specific chelator), or calpeptin (a calpain inhibitor). Furthermore, D7-induced [Ca{sup 2+}]{sub c} was found to alter mitochondrial membrane potential and induce cytochrome c release, which was inhibited by either Bapta-AM or ruthenium red (an inhibitor of mitochondrial Ca{sup 2+} uniporter). Thus, these results provided a deeper insight into the D7-induced redox signaling which eventually integrated the calcium-dependent calpain/caspase12 activation and mitochondrial alterations to accentuate the induction of apoptotic cell death.

  9. A novel synthesis of carbon-labelled quinolone-3-carboxylic acid antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Carr, R.M.; Sutherland, D.R. (Glaxo Research and Development Ltd., Greenford (United Kingdom). Isotope Chemistry Group)

    1994-10-01

    3-Iodoquinolones were prepared from the corresponding quinolone-3-carboxylic acids by Hunsdiecker-type iododecarboxylation reactions with lead tetraacetate and iodine. Cyanation of the iodo compounds with mixtures of potassium [[sup 13]C]cyanide and copper (1) iodide, gave [3-[sup 13]C]cyanoquinolones which on acidic hydrolysis afforded quinolone-[3-[sup 13]C]carboxylic acids. In this way, nalidixic acid, an immediate precursor of norfloxacin, and quinolone WIN57273 were labelled with carbon-13 in the metabolically stable carboxylic acid fragment. (author).

  10. New luminophor-activators based on (fluoro)quinolone antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, A.V. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Karaseva, E.T. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Korpela, T. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Karasev, V.E. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation)], E-mail: karasev@ich.dvo.ru

    2008-11-15

    It was shown that (fluoro)quinolone antibiotics form strongly fluorescent solid-state complexes with Eu(III) and Tb(III) lanthanide ions, with a wavelength red-shift beneficial for applications to greenhouse-cover polymers. Complexes with optimal properties were prepared by the mechanical activation of fine-dispersed composite mixtures with the lanthanide salts. The spectral properties, photo-stability to UV-light, and compatibility with the polyethylene matrix were investigated. The formulation additives of the tablet forms of the antibiotic medicines did not quench the fluorescence from the lanthanide ions. Therefore, the outdated drug forms of the antibiotics can serve as cheap recyclable sources for the covering material of greenhouses. In addition, diphenylguanidine (DPG) was investigated as a coligand. DPG enhanced fluorescence of the fluoroquinolone complexes by decreasing the non-radiative energy loss through O-H vibration of H{sub 2}O.

  11. Quinolones for the Treatment of Neisseria Gonorrhoeae and Chlamydia Trachomatis

    Directory of Open Access Journals (Sweden)

    Sebastian Faro

    1993-01-01

    Full Text Available The most commonly sexually transmitted bacteria are Neisseria gonorrhoeae and Chlamydia trachomatis. The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment of N. gonorrhoeae and C. trachomatis cervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID. Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

  12. Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids

    Directory of Open Access Journals (Sweden)

    Tabunoki Hiroko

    2012-04-01

    Full Text Available Abstract Background Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a and renieramycin M (RM; the compound 2a from Thai marine invertebrates, together with a 2’-N-4”-pyridinecarbonyl derivative of ET-770 (the compound 3. We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG. Methods We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics. Results All of these compounds induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B. Conclusion Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective

  13. Medicinal Plants: Their Use in Anticancer Treatment

    OpenAIRE

    Greenwell, M.; Rahman, P.K.S.M.

    2015-01-01

    Globally cancer is a disease which severely effects the human population. There is a constant demand for new therapies to treat and prevent this life-threatening disease. Scientific and research interest is drawing its attention towards naturally-derived compounds as they are considered to have less toxic side effects compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activ...

  14. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

    Science.gov (United States)

    Kocsis, Bela; Domokos, J; Szabo, D

    2016-01-01

    Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future. PMID:27215369

  15. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

    OpenAIRE

    COŞKUN, Demet; Tekin, Suat; SANDAL, Süleyman; Coşkun, Mehmet Fatih

    2016-01-01

    Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3a–f), were designed, synthesized, and characterized. In vitro antitu...

  16. Evaluating the impact of a novel restricted reimbursement policy for quinolone antibiotics: A time series analysis

    Directory of Open Access Journals (Sweden)

    Manns Braden

    2012-08-01

    Full Text Available Abstract Background Publicly-funded drug plans often use prior authorization policies to limit drug prescribing. To guide physician prescribing of a class of antibiotics with broad antimicrobial activity (quinolone antibiotics in accordance with new prescribing guidelines, Alberta’s provincial health ministry implemented a new mechanism for formulary restriction entitled the optional special authorization (OSA program. We conducted an observational study to determine the impact of this new formulary restriction policy on antimicrobial prescription rates as well as any clinical consequences. Methods Quinolone antibiotic use, and adherence with quinolone prescribing guidelines, was assessed before and after implementation of the OSA program in patients with common outpatient infections using an administrative data cohort and a chart review cohort, respectively. At the same time this policy was implemented to limit quinolone prescribing, two new quinolone antibiotics were added to the formulary. Using administrative data, we analysed a total of 397,534 unique index visits with regard to overall antibiotic utilization, and through chart review, we analysed 1681 charts of patients with infections of interest to determine the indications for quinolone usage. Results Using segmented regression models adjusting for age, sex and physician enrollment in the OSA program, there was no statistically significant change in the monthly rate of all quinolone use (−3.5 (95% CI −5.5, 1.4 prescriptions per 1000 index visits following implementation of the OSA program (p = 0.74. There was a significant level change in the rate of quinolone antibiotic use for urinary tract infection (−33.6 (95% CI: -23.8, -43.4 prescriptions and upper respiratory tract infection (−16.1 (95%CI: -11.6, -20.6 prescriptions per 1000 index visits. Among quinolone prescriptions identified on chart review, 42.5% and 58.5% were consistent with formulary guidelines before and

  17. Recurrent mania consequent to quinolones exposure: A case report and review of literature.

    Science.gov (United States)

    Sahoo, Swapnajeet; Aneja, Jitender; Basu, Debasish

    2016-01-01

    Antibiotics are the one of the most commonly used group, of drugs, in general medical and surgical practice. The quinolone antibiotics can lead to a range of adverse neuropsychiatric effects with most of the reports due to ciprofloxacin and ofloxacin. Here, we report an interesting and rarely described psychiatric manifestation of recurrent mania following the use of quinolone antibiotics, and briefly review the available literature. PMID:27453864

  18. Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.

    Directory of Open Access Journals (Sweden)

    Ross J Davidson

    Full Text Available BACKGROUND: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. METHODS: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB. Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR mutations. RESULTS: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01. Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. CONCLUSIONS: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.

  19. DNA Gyrase Is the Target for the Quinolone Drug Ciprofloxacin in Arabidopsis thaliana*

    Science.gov (United States)

    Evans-Roberts, Katherine M.; Mitchenall, Lesley A.; Wall, Melisa K.; Leroux, Julie; Mylne, Joshua S.; Maxwell, Anthony

    2016-01-01

    The Arabidopsis thaliana genome contains four genes that were originally annotated as potentially encoding DNA gyrase: ATGYRA, ATGYRB1, ATGYRB2, and ATGYRB3. Although we subsequently showed that ATGYRB3 does not encode a gyrase subunit, the other three genes potentially encode subunits of a plant gyrase. We also showed evidence for the existence of supercoiling activity in A. thaliana and that the plant is sensitive to quinolone and aminocoumarin antibiotics, compounds that target DNA gyrase in bacteria. However, it was not possible at that time to show whether the A. thaliana genes encoded an active gyrase enzyme, nor whether that enzyme is indeed the target for the quinolone and aminocoumarin antibiotics. Here we show that an A. thaliana mutant resistant to the quinolone drug ciprofloxacin has a point mutation in ATGYRA. Moreover we show that, as in bacteria, the quinolone-sensitive (wild-type) allele is dominant to the resistant gene. Further we have heterologously expressed ATGYRA and ATGYRB2 in a baculovirus expression system and shown supercoiling activity of the partially purified enzyme. Expression/purification of the quinolone-resistant A. thaliana gyrase yields active enzyme that is resistant to ciprofloxacin. Taken together these experiments now show unequivocally that A. thaliana encodes an organelle-targeted DNA gyrase that is the target of the quinolone drug ciprofloxacin; this has important consequences for plant physiology and the development of herbicides. PMID:26663076

  20. [Multiresidue determination of quinolones in animal and fishery products by HPLC].

    Science.gov (United States)

    Chonan, Takao; Fujimoto, Toru; Inoue, Maki; Tazawa, Teijiro; Ogawa, Hiroshi

    2008-06-01

    A simple and rapid multiresidue method was developed for the determination of twelve quinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, nalidixic acid, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid and sarafloxacin) in muscle, liver, chicken eggs, milk, prawn and rainbow trout. The quinolones were extracted from a sample with acetonitrile-water (95 : 5). A fifth part of the filtered extract was diluted with water to keep the acetonitrile ratio at ca. 60%, and passed through a C18 mini-column. The eluate was evaporated to dryness, and the residues were dissolved in methanol-water (30 : 70) for HPLC analysis. The quinolones were separated on a Inertsil ODS-3V column (4.6 mm i.d.x250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with fluorescence detection.No interfering peak was found on the chromatograms of animal and fishery products, except for milk. The recoveries of the quinolones were over 60% from the animal and fishery products fortified at 0.1 microg/g, and the quantification limits of the quinolones were 0.005 microg/g. This proposed method was found to be effective and suitable for the screening of the quinolones in animal and fishery products.

  1. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

    Directory of Open Access Journals (Sweden)

    Jérémie Piton

    Full Text Available Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

  2. Synthesis and biological evaluation of novel hybrid matrine derivatives as anticancer agents%新型苦参碱衍生物杂合体的合成及抗肿瘤活性

    Institute of Scientific and Technical Information of China (English)

    何黎琴; 杨琦; 顾宏霞; 张奕华; 王效山

    2012-01-01

    Matrine,one of the major active alkaloids isolated from the Sophora alopecuroides L which is a useful Chinese herbal drug, possesses antipyretic, anti-inflammatory, analgesic and notable antiviral activities , and has been used for the treatment of lipopolysaccharide-induced liver injury. Recently, it bas been reported that matrine could inhibit the growth of tumor cells. Nitric oxide(NO) ,a free radical molecule,is involved in numerous physiological and pathological processes, with high levels NO usually are toxic to tumor cells. It was therefore of interest to determine whether the hybrid of matrine and NO donor furoxan would provide a hitherto unknown class of matrine derivatives that possess potent anticancer activity. Herein 14 hybrid matrine derivatives conjugated with nitric oxide (NO) donor were designed and synthesized based on molecular hybridization strategy. All target compounds were evaluated for anti-proliferative activity against human hepatocellular HepG2 cells in vitro by MTT method. The results indicated that all of these compounds had potent anti-proliferative activity which were more potent than their parent compounds.%目的 为进一步提高苦参碱的抗肿瘤活性,基于分子杂合策略,设计合成N-苄基苦参酸一氧化氮杂合体衍生物,并对其体外抗肿瘤活性进行初步研究.方法 将NO供体硝酸酯通过连接基团与N-苄基苦参酸的羧基连接制得NO供体型N-苄基苦参酸衍生物.采用MTT法测定了目标化合物对人肝癌细胞(HepG2)增殖的体外抑制活性.结果与结论 合成了14个结构新颖的N-苄基苦参酸一氧化氮杂合体衍生物,其结构经MS、IR、1H-NMR确证,且目标化合物均具有较苦参碱强的增殖抑制活性.

  3. Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli.

    Science.gov (United States)

    Martín-Gutiérrez, Guillermo; Rodríguez-Beltrán, Jerónimo; Rodríguez-Martínez, José Manuel; Costas, Coloma; Aznar, Javier; Pascual, Álvaro; Blázquez, Jesús

    2016-07-01

    Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs. PMID:27139482

  4. Study of fluorescence characteristics of the charge-transfer reaction of quinolone agents with bromanil

    Science.gov (United States)

    Li, Wen-Ying; Chen, Xiao-Fang; Xuan, Chun-Sheng

    2009-01-01

    A spectrofluorimetric method was discussed for the determination of three antibacterial quinolone derivatives, ofloxacin (OFL), norfloxacin (NOR) and ciprofloxacin (CIP) through charge-transfer complexation (CTC) with 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil, TBBQ). The method was based on the reaction of these drugs as n-electron donors with the π-acceptor TBBQ. TBBQ was found to react with these drugs to produce a kind of yellow complexes and the fluorescence intensities of the complexes were enhanced by 29-36 times more than those of the corresponding monomers. UV-vis, 1H NMR and XPS techniques were used to study the complexes formed. The various experimental parameters affecting the fluorescence intensity were studied and optimized. Under optimal reaction conditions, the rectilinear calibration graphs were obtained in the concentration range of 0.021-2.42 μg mL -1, 0.017-2.63 μg mL -1 and 0.019-2.14 μg mL -1 for OFL, NOR and CIP, respectively. The methods developed were applied successfully to the determination of the subject drugs in their pharmaceutical dosage forms with good precision and accuracy compared to official and reported methods as revealed by t- and F-tests.

  5. A Function of SmeDEF, the Major Quinolone Resistance Determinant of Stenotrophomonas maltophilia, Is the Colonization of Plant Roots

    OpenAIRE

    García-León, Guillermo; Hernández, Alvaro; Hernando-Amado, Sara; Alavi, Peyman; Berg, Gabriele; Martínez, José Luis

    2014-01-01

    Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient e...

  6. Quinolone resistance in absence of selective pressure: the experience of a very remote community in the Amazon forest.

    Directory of Open Access Journals (Sweden)

    Lucia Pallecchi

    Full Text Available BACKGROUND: Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002. METHODS: The community exhibited a considerable level of geographical isolation, limited contact with the exterior and minimal antibiotic use (not including quinolones. In December 2009, fecal carriage of antibiotic resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in 48 animals reared in the community. All fluoroquinolone-resistant isolates were genotyped and characterized for the mechanisms of plasmid- and chromosomal-mediated quinolone resistance. PRINCIPAL FINDINGS: Despite the characteristics of the community remained substantially unchanged during the period 2002-2009, carriage of quinolone-resistant E. coli was found to be common in 2009 both in humans (45% nalidixic acid, 14% ciprofloxacin and animals (54% nalidixic acid, 23% ciprofloxacin. Ciprofloxacin-resistant isolates of human and animal origin showed multidrug resistance phenotypes, a high level of genetic heterogeneity, and a combination of GyrA (Ser83Leu and Asp87Asn and ParC (Ser80Ile substitutions commonly observed in fluoroquinolone-resistant clinical isolates of E. coli. CONCLUSIONS: Remoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli. Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation. Interventions aimed at reducing the spreading of resistant isolates (by improving sanitation

  7. Influence Of Quinolone Lethality on Irradiated Anaerobic Growth of Escherichia Coli

    International Nuclear Information System (INIS)

    Bacteriostatic and bactericidal activities were measured with wild type cells and isomerase mutants of Escherichia coli for ciprofloxacin, formation of quinolone-gyrase-DNA complexes, observed as a sodium dodecyl sulfate (SDS) dependent drop in cell lysate viscosity, occurred during aerobic and anaerobic growth and in the presence and in the absence of chloramphenicol. Quinolone activity against Escherichia coli was examined during aerobic growth, aerobic treatment with chloramphenicol, and anaerobic growth. Nalidixic acid, norfloxacin and ciprofloxacin were lethal for cultures growing aerobically, and the bacteriostatic activity of each quinolone was unaffected by anaerobic growth. However, lethal activity was distinct for each quinolone with cells treated aerobically with chloramphenicol or grown anaerobically. Nalidixic acid failed to kill cells under both conditions, norfloxacin killed cells when they were grown anaerobically but not when they were treated with chloramphenicol, ciprofloxacin killed cells under both conditions but required higher concentrations than those required with cells grown aerobically, C-methoxy fluoro quinolone was equally lethal under all conditions. However, lethal chromosome fragmentation, detected as a drop in viscosity in the absence of SDS, was occurred with nalidixic acid treatment only under aerobic conditions in the absence of chloramphenicol, thus, all quinolones tested appeared to form reversible bacteriostatic complexes containing broken DNA during aerobic growth, during anaerobic growth, and when protein synthesis is blocked. The ability to fragment chromosomes rapidly kill cells under these conditions depends on quinolone structure. The radiation of sublethal dose was 3 Gy at rate of 0.6 Gy/min was shown as non-significant result

  8. Mechanisms of quinolone resistance and implications for human and animal health

    Directory of Open Access Journals (Sweden)

    Velhner Maja

    2010-01-01

    Full Text Available Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance. The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .

  9. Melatonin Anticancer Effects: Review

    Directory of Open Access Journals (Sweden)

    Luigi Di Bella

    2013-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  10. Effect of various storage conditions on the stability of quinolones in raw milk.

    Science.gov (United States)

    Chen, Meixia; Wen, Fang; Wang, Hui; Zheng, Nan; Wang, Jiaqi

    2016-07-01

    Research on the storage stability of antibiotic residues in milk is important for method development or validation, milk quality control and risk assessment during screening, confirmation, qualitative or quantitative analysis. This study was conducted using UPLC-MS/MS to determine the stability of six quinolones - ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), difloxacin (DIF) and flumequine (FLU) - in raw milk stored under various conditions to investigate if quinolones degrade during storage of milk, and finally to determine optimal storage conditions for analysis and scientific risk assessment of quinolone residues in raw milk. The storage conditions included different temperatures and durations (4°C for 4, 8, 24 and 48 h; -20°C for 1, 7 and 30 days; -80°C for 1, 7 and 30 days), thawing temperatures (25, 40 and 60°C), freeze-thaw cycles (1-5), and the addition of different preservatives (sodium thiocyanate, sodium azide, potassium dichromate, bronopol and methanal). Most quinolones exhibited high stability at 4°C for up to 24 h, but began to degrade after 48 h. In addition, no degradation of quinolones was seen when milk samples were stored at -20°C for up to 7 days; however, 30 days of storage at -20°C resulted in a small amount of degradation (about 30%). Similar results were seen when samples were stored at -80°C. Moreover, no losses were observed when frozen milk samples were thawed at 25, 40 or 60°C. All the quinolones of interest, except sarafloxacin, were stable when milk samples were thawed at 40°C once and three times, but unstable after five freeze-thaw cycles. Preservatives affected the stability of quinolones, but the effects differed depending on the preservative and quinolone. The results of this study indicate optimum storage protocols for milk samples, so that residue levels reflect those at the time of initial sample analysis, and should improve surveillance programmes for quinolones in raw milk

  11. Molecular characterisation of quinolone-resistant Shigella strains isolated in Tehran, Iran.

    Science.gov (United States)

    Ranjbar, Reza; Behnood, Vahid; Memariani, Hamed; Najafi, Ali; Moghbeli, Majid; Mammina, Caterina

    2016-06-01

    Over the past few years, the number of Shigella strains resistant to nalidixic acid has increased and has made the selection of effective antimicrobial therapy more difficult. The purpose of this study was to investigate the molecular mechanism of quinolone resistance in Shigella strains. Shigella strains isolated from 1100 diarrhoeal patients in Tehran, Iran, were assessed for their susceptibility to nalidixic acid prior to PCR-RFLP and sequence analysis of their quinolone resistance genes. Among 73 Shigella strains isolated, 23 (31.5%) were resistant to nalidixic acid. The most common Shigella spp. was Shigella sonnei (54; 74.0%). Of the 23 quinolone-resistant isolates, 4 (17.4%) (including 2 Shigella flexneri, 1 S. sonnei and 1 Shigella boydii) contained the qnrS gene. However, none of the isolates harboured qnrA or qnrB genes. PCR-RFLP analysis of gyrA showed a mutation profile in two nalidixic acid-resistant strains, including one S. sonnei and one S. flexneri. Sequencing of mutant gyrA genes revealed a point mutation at position 83, resulting in the replacement of serine by leucine. In conclusion, molecular mechanisms of resistance to quinolones were identified in 6 of 23 Shigella isolates. Other possible mechanisms of resistance should also be investigated for better characterisation of quinolone-resistant Shigella isolates. PMID:27436462

  12. Study of the luminescence behavior of seven quinolones on a paper substrate

    Energy Technology Data Exchange (ETDEWEB)

    Li Junfen [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: fenjunli@sina.com; Li Jianqing [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Shuang Shaomin [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Dong Chuan [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: dc@sxu.edu.cn

    2005-08-29

    Studies on the luminescence spectra behaviors of seven quinines on solid substrate (SS-RTP) were performed. Experimental conditions, such as heavy atom type, pH and drying time of the sample, etc. on solid substrate room temperature phosphorescence (SS-RTP) or solid substrate delayed fluorescence (SS-DF), were studied in detail. CdCl{sub 2} could induce strongest RTP or DF emission of these quinolones. In addition, a comparative study on the spectral behavior of seven quinolones was given, including low temperature phosphorescence (LTP), low temperature fluorescence (LTF) and spectra methioned above. New determination methods for the analysis of seven quinolones by solid substrate room temperature fluorescence (SS-RTF), SS-RTP or SS-DF with filter paper as solid substrate were presented. Analytical characteristics of these methods of seven quinolones were studied. The linear dynamic ranges (LDR), the limit of detection (LOD) and the relative standard deviation (R.S.D.) were valued. Recoveries of seven quinolones in human urine samples were from 98.1% to 104.3%.

  13. Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids

    OpenAIRE

    Tabunoki Hiroko; Saito Naoki; Suwanborirux Khanit; Charupant Kornvika; Satoh Jun-ichi

    2012-01-01

    Abstract Background Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and ...

  14. Synthesis and Structure–Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell Lung Cancer

    OpenAIRE

    Dexheimer, Thomas S.; Rosenthal, Andrew S.; Luci, Diane K; Liang, Qin; Villamil, Mark A.; Chen, Junjun; Sun, Hongmao; Kerns, Edward H.; Simeonov, Anton; Jadhav, Ajit; Zhuang, Zhihao; Maloney, David J.

    2014-01-01

    Deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases including cancer. The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1), in association with UAF1 (USP1-associated factor 1), is a known regulator of DNA damage response and has been shown as a promising anticancer target. To further evaluate USP1/UAF1 as a therapeutic target, we conducted a quantitative high throughput screen of >400000 compounds and subsequent med...

  15. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

    Directory of Open Access Journals (Sweden)

    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  16. Gallium(iii) and iron(iii) complexes of quinolone antimicrobials.

    Science.gov (United States)

    Mjos, Katja Dralle; Cawthray, Jacqueline F; Polishchuk, Elena; Abrams, Michael J; Orvig, Chris

    2016-08-16

    Iron is an essential nutrient for many microbes. According to the "Trojan Horse Hypothesis", biological systems have difficulties distinguishing between Fe(3+) and Ga(3+), which constitutes the antimicrobial efficacy of the gallium(iii) ion. Nine novel tris(quinolono)gallium(iii) complexes and their corresponding iron(iii) analogs have been synthesized and fully characterized. Quinolone antimicrobial agents from three drug generations were used in this study: ciprofloxacin, enoxacin, fleroxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, oxolinic acid, and pipemidic acid. The antimicrobial efficacy of the tris(quinolono)gallium(iii) complexes was studied against E. faecalis and S. aureus (both Gram-positive), as well as E. coli, K. pneumonia, and P. aeruginosa (all Gram-negative) in direct comparison to the tris(quinolono)iron(iii) complexes and the corresponding free quinolone ligands at various concentrations. For the tris(quinolono)gallium(iii) complexes, no combinational antimicrobial effects between Ga(3+) and the quinolone antimicrobial agents were observed. PMID:27315225

  17. Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment and antibiotic resistance in Indochina

    Directory of Open Access Journals (Sweden)

    Satoru eSuzuki

    2012-02-01

    Full Text Available Southeast Asia has become the center of rapid industrial development and economic growth. However, this growth has far outpaced investment in public infrastructure, leading to the unregulated release of many pollutants, including wastewater-related contaminants such as antibiotics. Antibiotics are of major concern because they can easily be released into the environment from numerous sources, and can subsequently induce development of antibiotic-resistant bacteria. Recent studies have shown that for some categories of drugs this source-to-environment antibiotic resistance relationship is more complex. This review summarizes current understanding regarding the presence of quinolones, sulfonamides, and tetracyclines in aquatic environments of Indochina and the prevalence of bacteria resistant to them. Several noteworthy findings are discussed: 1 quinolone contamination and the occurrence of quinolone resistance are not correlated; 2 occurrence of the sul sulfonamide resistance gene varies geographically; and 3 microbial diversity might be related to the rate of oxytetracycline resistance.

  18. Plasmid-mediated quinolone resistance; interactions between human, animal and environmental ecologies

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    Laurent ePOIREL

    2012-02-01

    Full Text Available Resistance to quinolones and fluoroquinolones is being increasingly reported among human but also veterinary isolates during the last two to three decades, very likely as a consequence of the large clinical usage of those antibiotics. Even if the principle mechanisms of resistance to quinolones are chromosome-encoded, due to modifications of molecular targets (DNA gyrase and topoisomerase IV, decreased outer-membrane permeability (porin defect and overexpression of naturally-occurring efflux, the emergence of plasmid-mediated quinolone resistance (PMQR has been reported since 1998. Although these PMQR determinants confer low-level resistance to quinolones and/or fluoroquinolones, they are a favorable background for selection of additional chromosome-encoded quinolone resistance mechanisms. Different transferable mechanisms have been identified, corresponding to the production of Qnr proteins, of the aminoglycoside acetyltransferase AAC(6’-Ib-cr, or of the QepA-type or OqxAB-type efflux pumps. Qnr proteins protect target enzymes (DNA gyrase and type IV topoisomerase from quinolone inhibition (mostly nalidixic acid. The AAC(6’-Ib-cr determinant acetylates several fluoroquinolones, such as norfloxacin and ciprofloxacin. Finally, the QepA and OqxAB efflux pumps extrude fluoroquinolones from the bacterial cell. A series of studies have identified the environment to be a reservoir of PMQR genes, with farm animals and aquatic habitats being significantly involved. In addition, the origin of the qnr genes has been identified, corresponding to the waterborne species Shewanella sp. Altogether, the recent observations suggest that the aquatic environment might constitute the original source of PMQR genes, that would secondly spread among animal or human isolates.

  19. Prevalence of plasmid-mediated quinolone resistance determinants among oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina

    Directory of Open Access Journals (Sweden)

    Giovanna Rincon Cruz

    2013-11-01

    Full Text Available High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6'-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6'-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers.

  20. Novel application of Wiener vis-à-vis Szeged indices: Antitubercular activities of quinolones

    Indian Academy of Sciences (India)

    Vijay K Agarwal; Shahnaz Bano; Keshav C Mathur; Padmakar V Khadikar

    2000-04-01

    The paper gives a brief account of the recently introduced Szeged index (Sz). Using this index antitubercular activities of N-2,4-difluorophenyl quinolones are subjected to quantitative structure-activity relationship analysis. The potential of Sz related to the Wiener index (W) is critically discussed. In addition, Huckel molecular orbital energies: HOMO, LUMO and total were also used for comparing and modelling antitubercular activities of the quinolones. The results, based on univariate as well as multivariate regressions, have shown that W, Sz and total give better results and that the correlations improve in multivariate regression analyses.

  1. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T;

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  2. Coumarin: a promising scaffold for anticancer agents.

    Science.gov (United States)

    Kaur, Manjinder; Kohli, Swarandeep; Sandhu, Sonali; Bansal, Yogita; Bansal, Gulshan

    2015-01-01

    Coumarin enjoys an important place in drug discovery process due to its presence in diversity of biologically active compounds. Many compounds of plant origin are derivatives of coumarin. Taking these natural products as lead, research groups across the globe have designed and synthesized numerous coumarin analogues for treatment of varied diseases. Cancer is one of the dreadful chronic diseases, and many drugs are available for its treatment. However, due to heterogeneity of cancer, the search is still on to develop drugs for specific types of cancers. The present review is an attempt to study various coumarin derivatives of natural as well as synthetic origins, which are identified or developed for the treatment of different types of cancers. Herein, we have classified various anticancer coumarin derivatives on the basis of their origin as well as substitution around it. These are discussed under the headings of natural, semi-synthetic and synthetic coumarin derivatives. The synthetic coumarin derivatives are further classified as mono-, di- and poly-substituted and fused coumarin derivatives. Of the six positions available for substituents on coumarin nucleus, only three positions (C-3, C-4 and C-7) are exploited for the selection of functional groups appropriate for anticancer activity. The other positions (C-5, C-6 and C-8) are either unexplored or very less exploited. The present review is expected to provide the medicinal chemists a guide to choose new functional groups for substitution at different positions of coumarin nucleus for development of novel compounds for the treatment of a specific type of cancer.

  3. The DNA gyrase-quinolone complex. ATP hydrolysis and the mechanism of DNA cleavage

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    , S. C., and Maxwell, A. (1998) J. Biol. Chem. 269, 22606-22614). The kinetics of ATP hydrolysis via this pathway have been studied and found to differ from those of the reaction of the drug-free enzyme. The quinolone-characteristic ATPase rate is DNA-dependent and can be induced in the presence...

  4. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa.

    Science.gov (United States)

    Pesci, E C; Milbank, J B; Pearson, J P; McKnight, S; Kende, A S; Greenberg, E P; Iglewski, B H

    1999-09-28

    Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.

  5. Quinolone resistant campylobacter infections in Denmark: risk factors and clinical consequences

    DEFF Research Database (Denmark)

    Engberg, J.; Neimann, J.; Nielsen, E. M.;

    2004-01-01

    origin) was associated with a decreased risk. Typing data showed an association between strains from retail food products and broiler chickens and quinolone-sensitive domestically acquired C. jejuni infections. An association between treatment with a fluoroquinolone before stool-specimen collection and...

  6. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: Comparison of pefloxacin, ciprofloxacin, and ofloxacin

    International Nuclear Information System (INIS)

    Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts

  7. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves

    NARCIS (Netherlands)

    Hordijk, J.; Veldman, K.T.; Dierikx, C.M.; Essen-Zandbergen, van A.; Wagenaar, J.A.; Mevius, D.J.

    2012-01-01

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional dat

  8. Improved microbial screning assay for the detection of quinolone residues in poultry and eggs

    NARCIS (Netherlands)

    Pikkemaat, M.G.; Mulder, P.P.J.; Elferink, J.W.A.; Cocq, A.; Nielen, M.W.F.; Egmond, van H.J.

    2007-01-01

    An improved microbiological screening assay is reported for the detection of quinolone residues in poultry muscle and eggs. The method was validated using fortified tissue samples and is the first microbial assay to effectively detect enrofloxacin, difloxacin, danofloxacin, as well as flumequine and

  9. Plasmid-mediated quinolone resistance among non-typhi Salmonella enterica isolates, USA

    Science.gov (United States)

    We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella (NTS) spp. isolates from humans, food animals, and retail meat in the United States in 2007. Fifty-one (2.4%) of human isolates (n=2165), 5 (1.6%) of isolates from animal isolates (n=1915) an...

  10. [Determination of 25 quinolones in cosmetics by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Lin, Li; Zhang, Yi; Tu, Xiaoke; Xie, Liqi; Yue, Zhenfeng; Kang, Haining; Wu, Weidong; Luo, Yao

    2015-03-01

    An analytical method was developed for the simultaneous determination of 25 quinolones, including danofloxacin mesylate, enrofloxacin, flumequine, oxloinic acid, ciprofloxacin, sarafloxacin, nalidixic acid, norfloxacin, and ofloxacin etc in cosmetics using direct extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Cosmetic sample was extracted by acidified acetonitrile, defatted by n-hexane and separated on Poroshell EC-C18 column with gradient elution program using acetonitrile and water (both containing 0. 1% formic acid) as the mobile phases and analyzed by LC-ESI-MS/MS under the positive mode using multiple reaction monitoring (MRM). The interference of matrix was reduced by the matrix-matched calibration standard curve. The method showed good linearities over the range of 1-200 mg/kg for the 25 quinolones with good linear correlation coefficients (r ≥ 0.999). The method detection limit of the 25 quinolones was 1.0 mg/kg, and the recoveries of all analytes in lotion, milky and cream cosmetics matrices ranged from 87.4% to 105% at the spiked levels of 1, 5 and 10 mg/kg with the relative standard deviations (RSD) of 4.54%-19.7% (n = 6). The results indicated that this method is simple, fast and credible, and suitable for the simultaneous determination of the quinolones in the above three types of cosmetics.

  11. Generation and characterization of quinolone-specific DNA aptamers suitable for water monitoring.

    Science.gov (United States)

    Reinemann, C; Freiin von Fritsch, U; Rudolph, S; Strehlitz, B

    2016-03-15

    Quinolones are antibiotics that are accredited in human and veterinary medicine but are regularly used in high quantities also in industrial livestock farming. Since these compounds are often only incompletely metabolized, significant amounts contaminate the aquatic environment and negatively impact on a variety of different ecosystems. Although there is increasing awareness of problems caused by pharmaceutical pollution, available methods for the detection and elimination of numerous pharmaceutical residues are currently inefficient or expensive. While this also applies to antibiotics that may lead to multi-drug resistance in pathogenic bacteria, aptamer-based technologies potentially offer alternative approaches for sensitive and efficient monitoring of pharmaceutical micropollutants. Using the Capture-SELEX procedure, we here describe the selection of an aptamer pool with enhanced binding qualities for fluoroquinolones, a widely used group of antibiotics in both human and veterinary medicine. The selected aptamers were shown to detect various quinolones with high specificity, while specific binding activities to structurally unrelated drugs were not detectable. The quinolone-specific aptamers bound to ofloxacin, one of the most frequently prescribed fluoroquinolone, with high affinity (KD=0.1-56.9 nM). The functionality of quinolone-specific aptamers in real water samples was demonstrated in local tap water and in effluents of sewage plants. Together, our data suggest that these aptamers may be applicable as molecular receptors in biosensors or as catcher molecules in filter systems for improved monitoring and treatment of polluted water. PMID:26547431

  12. [Preliminary study on occurrence and health risk assessment of quinolone antibiotics in vegetables from Guangzhou, China].

    Science.gov (United States)

    Li, Yan-Wen; Zhang, Yan; Mo, Ce-Hui; Tai, Yi-Ping; Wu, Xiao-Lian; Wang, Ji-Yang; Su, Qing-Yun

    2010-10-01

    Quinolone antibiotics (QNs) including norfloxacin (NOR), enrofolxacin (ENR), ciprofloxacin (CIP) and lomefloxacin (LOM) in vegetable samples collected from Guangzhou were determined by high performance liquid chromatography (HPLC) coupled with fluorescent detector (FLD). The detected frequency of QNs was 96% in vegetables. The total concentration of quinolones (sigma QNs) detected in vegetable ranged from 1.0 microg/kg to 1 683.1 microg/kg (F.W.). Leafy vegetable topped the content of quinolones among the three types of vegetables, followed by the melon-fruit vegetable and rhizome vegetable. The detected frequency of the four quinolone antibiotics ranked as NOR > CIP > LOM > ENR. Except ENR, concentrations of CIP, NOR, LOM and sigma QNs in pollution-free vegetable, green vegetable and organic vegetable were higher than those in routine cultivated vegetables. The maximum contribution to ADI value (caculated by the sum of CIP and ENR) is estimated up to 41.5% and 83% for adults and children respectively via consumption of vegetables.

  13. Characterization of quinolone resistance in Salmonella enterica serovar Indiana from chickens in China

    Science.gov (United States)

    The aim of this study was to characterize the quinolone resistance of Salmonella Indiana isolated from chickens in China. A total of 130 Salmonella isolates were obtained from chicken farms and slaughterhouses in the Shandong Province of China. All isolate serotypes were tested according to the Kauf...

  14. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: Comparison of pefloxacin, ciprofloxacin, and ofloxacin

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Elliott, T.B.; Ledney, G.D. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-05-01

    Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.

  15. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    Directory of Open Access Journals (Sweden)

    Alejandra eBernardini

    2015-10-01

    Full Text Available Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained S. maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457.. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  16. Triterpenoids of Marine Origin as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Yong-Xin Li

    2013-07-01

    Full Text Available Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads.

  17. Evaluating Medicinal Plants for Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Elisha Solowey

    2014-01-01

    Full Text Available Plants have been used for medical purposes since the beginning of human history and are the basis of modern medicine. Most chemotherapeutic drugs for cancer treatment are molecules identified and isolated from plants or their synthetic derivatives. Our hypothesis was that whole plant extracts selected according to ethnobotanical sources of historical use might contain multiple molecules with antitumor activities that could be very effective in killing human cancer cells. This study examined the effects of three whole plant extracts (ethanol extraction on human tumor cells. The extracts were from Urtica membranacea (Urticaceae, Artemesia monosperma (Asteraceae, and Origanum dayi post (Labiatae. All three plant extracts exhibited dose- and time-dependent killing capabilities in various human derived tumor cell lines and primary cultures established from patients’ biopsies. The killing activity was specific toward tumor cells, as the plant extracts had no effect on primary cultures of healthy human cells. Cell death caused by the whole plant extracts is via apoptosis. Plant extract 5 (Urtica membranacea showed particularly strong anticancer capabilities since it inhibited actual tumor progression in a breast adenocarcinoma mouse model. Our results suggest that whole plant extracts are promising anticancer reagents.

  18. A series of 2D metal–quinolone complexes: Syntheses, structures, and physical properties

    International Nuclear Information System (INIS)

    Six novel 2D metal–quinolone complexes, namely [Cd(cfH)(bpdc)]·H2O (1), [M(norfH)(bpdc)]·H2O (M=Cd (2) and Mn (3)), [Mn2(cfH)(odpa)(H2O)3]·0.5H2O (4), [Co2(norfH)(bpta)(μ2-H2O)(H2O)2]·H2O (5) and [Co3(saraH)2(Hbpta)2(H2O)4]·9H2O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4′-biphenyldicarboxylate, odpa=4,4′-oxydiphthalate, bpta=3,3′,4,4′-biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1–3 consist of 2D arm-shaped layers based on the 1D {M(COO)}nn+ chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal–quinolone complexes with 2D bilayer structure. By inspection of the structures of 1–6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal–quinolone complexes. The magnetic properties of compounds 3–6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1–2 are discussed. - Graphical abstract: Six novel 2D metal–quinolone complexes have been prepared by self-assemblies of the quinolones and metal salts in the presence of long aromatic polycarboxylates. Highlights: ►Compounds 1–3 consist of novel 2D arm-shaped layers based on the 1D {M(COO)}nn+ chains. ► Compounds 4 and 5 are two novel 2D layers based on tetranuclear Mn or Co clusters with kgd topology. ► Compound 6 is the first example of metal–quinolone complexes with 2D bilayer structure. ► Compounds 1–6 represent six unusual examples of 2D metal–quinolone complexes.

  19. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Energy Technology Data Exchange (ETDEWEB)

    He, Jiang-Hong [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Xiao, Dong-Rong, E-mail: xiaodr98@yahoo.com.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Luo, Qun-Li, E-mail: qlluo@swu.edu.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Wang, En-Bo, E-mail: wangeb889@nenu.edu.cn [Key Laboratory of Polyoxometalate Science of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024 (China)

    2013-02-15

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]{center_dot}H{sub 2}O (1), [M(norfH)(bpdc)]{center_dot}H{sub 2}O (M=Cd (2) and Mn (3)), [Mn{sub 2}(cfH)(odpa)(H{sub 2}O){sub 3}]{center_dot}0.5H{sub 2}O (4), [Co{sub 2}(norfH)(bpta)({mu}{sub 2}-H{sub 2}O)(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O (5) and [Co{sub 3}(saraH){sub 2}(Hbpta){sub 2}(H{sub 2}O){sub 4}]{center_dot}9H{sub 2}O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4 Prime -biphenyldicarboxylate, odpa=4,4 Prime -oxydiphthalate, bpta=3,3 Prime ,4,4 Prime -biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed. - Graphical abstract: Six novel 2D metal-quinolone complexes have been prepared by self-assemblies of the quinolones and metal salts in the presence of long aromatic polycarboxylates. Highlights: Black-Right-Pointing-Pointer Compounds 1-3 consist of novel 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Black-Right-Pointing-Pointer Compounds 4 and 5 are two novel 2D layers based on tetranuclear Mn or Co clusters with kgd topology. Black-Right-Pointing-Pointer Compound 6 is the first example of metal-quinolone complexes with 2D bilayer structure. Black-Right-Pointing-Pointer Compounds 1-6 represent six unusual

  20. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jin-Jian Lu

    2012-01-01

    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  1. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

    Directory of Open Access Journals (Sweden)

    Narah Merina

    2012-06-01

    Full Text Available Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against cancer. Some of the lead molecules isolated from different medicinal plants are already in use to treat cancer and chemotherapeutic side effects. These potential and successful anticancer molecules include Vincristine, Vinblastin, Taxol, Camptothecin and Podophyllotoxin. This paper deals with the selective medicinal plants having anticancer properties which could be further designed to produce cancer curing drugs.

  2. Anti-cancer natural products isolated from chinese medicinal herbs

    Directory of Open Access Journals (Sweden)

    Wu Guosheng

    2011-07-01

    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  3. Sub-inhibitory concentrations of vancomycin prevent quinolone-resistance in a penicillin-resistant isolate of Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Moreillon Philippe

    2001-07-01

    Full Text Available Abstract Background The continuous spread of penicillin-resistant pneumococci represents a permanent threat in the treatment of pneumococcal infections, especially when strains show additional resistance to quinolones. The main objective of this study was to determine a treatment modality impeding the emergence of quinolone resistance. Results Exposure of a penicillin-resistant pneumococcus to increasing concentrations of trovafloxacin or ciprofloxacin selected for mutants resistant to these drugs. In the presence of sub-inhibitory concentrations of vancomycin, development of trovafloxacin-resistance and high-level ciprofloxacin-resistance were prevented. Conclusions Considering the risk of quinolone-resistance in pneumococci, the observation might be of clinical importance.

  4. Discovery of Natural Product Anticancer Agents from Biodiverse Organisms

    OpenAIRE

    Kinghorn, A. Douglas; Chin, Young-Won; Swanson, Steven M.

    2009-01-01

    For over 40 years, small organic molecules derived naturally from microbes and plants have provided a number of useful cancer chemotherapeutic drugs. The search for naturally occurring lead compounds of this type has continued in recent years, with the constituents of marine fauna and flora as well as those of terrestrial microorganisms and plants being investigated for their anti-cancer activities. In the present short review, selected new compounds or their derivatives are described that ha...

  5. Classification of current anticancer immunotherapies

    Science.gov (United States)

    Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

    2014-01-01

    During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

  6. Artemisinin–Second Career as Anticancer Drug?

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2015-10-01

    Full Text Available Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L. represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.g. expression of antioxidant response genes, cell cycle arrest (G1 as well as G2 phase arrests, DNA damage that is repaird by base excision repair, homogous recombination and non-homologous end-joining, as well as different modes of cell death (intrinsic and extrinsic apoptosis, autophagy, necrosis, necroptosis, oncosis, and ferroptosis. Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc. and signaling pathways are affected by artemisinins (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others. Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients. Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs.

  7. Efficacy of a non-hypercalcemic vitamin-D2 derived anti-cancer agent (MT19c and inhibition of fatty acid synthesis in an ovarian cancer xenograft model.

    Directory of Open Access Journals (Sweden)

    Richard G Moore

    Full Text Available BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3 xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K activity independently of PPAR-gamma protein. SIGNIFICANCE: Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.

  8. Mechanistic study of electrochemical oxidation of catechols in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)]. E-mail: a-zavareh@sbu.ac.ir; Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Moghaddam, Abdolmajid Bayandori [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)

    2005-09-20

    Electrochemical oxidation of catechols (1a-1c) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a-1c) participate in Michael addition reactions with 3 to form the corresponding benzofuran (or isochromeno[4,3-c]quinoline) derivatives (6a-6c). The electrochemical synthesis of (6a-6c) has been successfully performed in an undivided cell in good yield and purity. The oxidation mechanism was deduced from voltammetric data and by coulometry at controlled-potential. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  9. Mechanistic study of electrochemical oxidation of o-dihydroxybenzenes in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Moghaddam, Abdolmajid Bayandori [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of)]. E-mail: bayandori@gmail.com; Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of); Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of); Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Davarani, Saied Saeed Hosseiny [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of)

    2005-11-01

    Electrochemical oxidation of o-dihydroxybenzenes (1a and 1b) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-quinones derived from o-dihydroxybenzenes (1a and 1b) participate in 1,4-(michael) addition reactions with 3 to form the corresponding new o-dihydroxybenzene derivatives (6a and 6b). We propose a mechanism for the electrode process. The efficient electrochemical synthesis of 6a and 6b has been successfully performed at carbon rod electrodes in an undivided cell in good yield and purity. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  10. Anticancer agents from marine sponges.

    Science.gov (United States)

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  11. 喹诺酮类药物的研究进展%Progress on the Research of Pharmaceuticals of Quinolones

    Institute of Scientific and Technical Information of China (English)

    曾焕君; 王怀生

    2014-01-01

    Quinolones are synthetic antibacterial agents. many quinolones have one or two chiral centers and some of enantiomers show dif erent feature in pharmacology, toxicology and pharmacodynamics. In this paper, chiral separation and determination of quinolones about recent years were reviewed for providing some reference in the research of quinolones.%喹诺酮类药物是人工合成的抗菌药,很多药物都具有1~2个手性中心,且有些对映体呈现不同的药理学的、毒理学的、药效学的特性。本文对近几年喹诺酮类的药物手性的拆分与定量进行了研究,为临床上研究喹诺酮类的药物提供了一系列参考依据。

  12. Current developments of coumarin-based anti-cancer agents in medicinal chemistry.

    Science.gov (United States)

    Emami, Saeed; Dadashpour, Sakineh

    2015-09-18

    Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure-activity relationship of the most potent compounds. PMID:26318068

  13. Current developments of coumarin-based anti-cancer agents in medicinal chemistry.

    Science.gov (United States)

    Emami, Saeed; Dadashpour, Sakineh

    2015-09-18

    Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure-activity relationship of the most potent compounds.

  14. Geldanamycin and its anti-cancer activities.

    Science.gov (United States)

    Fukuyo, Yayoi; Hunt, Clayton R; Horikoshi, Nobuo

    2010-04-01

    Geldanamycin is a benzoquinone ansamycin antibiotic that manifests anti-cancer activity through the inhibition of HSP90-chaperone function. The HSP90 molecular chaperone is expressed at high levels in a wide variety of human cancers including melanoma, leukemia, and cancers in colon, prostate, lung, and breast. In cancer cells dependent upon mutated and/or over-expressed oncogene proteins, HSP90 is thought to have a critical role in regulating the stability, folding, and activity of HSP90-associated proteins, so-called "client proteins". These client proteins include the growth-stimulating proteins and kinases that support malignant transformation. Recently, oncogenic activating BRAF mutants have been identified in variety of cancers where constitutive activation of the MEK/ERK MAPK signaling pathway is the key for tumorigenesis, and they have been shown to be client proteins for HSP90. Accordingly, HSP90 inhibition can suppress certain cancer-causing client proteins and therefore represents an important therapeutic target. The molecular mechanism underlying the anti-cancer effect of HSP90 inhibition is complicated. Geldanamycin and its derivatives have been shown to induce the depletion of mutationally-activated BRAF through several mechanisms. In this review, we will describe the HSP90-inhibitory mechanism, focusing on recent progress in understanding HSP90 chaperone structure-function relationships, the identification of new HSP90 client proteins and the development of HSP90 inhibitors for clinical applications.

  15. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.;

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  16. Comparative Analysis of Quinolone Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli from Chinese Children and Adults

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2015-01-01

    Full Text Available The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P>0.05. The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P=0.5444. Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

  17. Anticancer activity of Amauroderma rude.

    Directory of Open Access Journals (Sweden)

    Chunwei Jiao

    Full Text Available More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities.

  18. Determination of fluorinated quinolone antibacterials by ion chromatography with fluorescence detection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan-zhen; ZHANG Zheng-yi; ZHOU Yan-chun; LIU Li; ZHU Yan

    2007-01-01

    For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluorescence detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column with an eluent of 15 mmol/L H2SO4 and 35% methanol (v/v) at a flow-rate of 1.0 ml/min and detected with fluorescence with excitation and emission wave lengths of 347 nm and 420 nm respectively. The detection limits (S/N=3) ofnorfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively. The relative standard deviations of retention time, peak area and peak height were less than 1.1% and good linear relationship resulted.The developed method was applied to pharmaceutical formulations and biological fluids.

  19. An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype typhimurium DT104

    DEFF Research Database (Denmark)

    Molbak, K.; Baggesen, Dorte Lau; Aarestrup, Frank Møller;

    1999-01-01

    tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones. Methods The Danish salmonella surveillance program determines the phage types of all typhimurium strains from the food chain, and in the case of suspected outbreaks, five-drug-resistant strains are...... findings here. Results Until 1997, DT104 infections made up less than 1 percent of all human salmonella infections. The strain isolated from patients in the first community outbreak of DT104 in Denmark, in 1998, was resistant to nalidixic acid and had reduced susceptibility to fluoroquinolones. The...... fluoroquinolones. Conclusions Our investigation of an outbreak of DT104 documented the spread of quinolone-resistant bacteria from food animals to humans; this spread was associated with infections that were difficult to treat. Because of the increase in quinolone resistance in salmonella, the use of...

  20. Survey of Tetracyclines, Sulfonamides, Sulfamethazine, and Quinolones in UHT Milk in China Market

    Institute of Scientific and Technical Information of China (English)

    HAN Rong-wei; ZHENG Nan; WANG Jia-qi; ZHEN Yun-peng; LI Song-li; YU Qun-li

    2013-01-01

    This study surveyed 180 samples of ultra high temperature (UHT) milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were<1.5, 26.2, 22.6, and 58.8μg kg-1, respectively. None of the samples exceeded the maximum residue levels (MRLs) for these four veterinary drugs, according to the regulations set by China, the European Union (EU) and the Codex Alimentarius Commission (CAC).

  1. "Changes in cartilage of rats after treatment with Quinolone and in Magnesium-deficient diet "

    Directory of Open Access Journals (Sweden)

    Shakibaei M

    2002-07-01

    Full Text Available Ultrastructural changes in immature articular carilage were studied after treatment of 5-weeks-old rats with ofloxacin, a fluoroquinolone, and in magnesium deficiency.We concluded that quinolone-induced arthropathy is probably due to chelation of functionally available magnesium in joint cartilage as magnesium deficiency in joint cartilage could impair chondrocyte-matrix- interaction which is mediated by cation-dependent integrin-receptors of the β1-subfamily. With immuno-histochemical methods using monoclonal and polyclonal antibodies we showed that B1 integrins were expressed in rat joint cartilage. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2×600 mg ofloxacin/kg body wt for one day. Gross-structural lesions (e.g. cleft formation, unmasked collagen fibres in magnesium deficient rats were very similar but changes in intergrin expression were less pronounced. Alterations observed on the ultrastructural level showed striking similarities in magnesium-deficient rats and in rats treated with single doses of 600 mg ofloxacin per kg body wt.Typical observation were: bundle shaped, electron-dense aggregates on the surface and in the cytoplasm of chondrocytes, detachement of the cell membrance from the matrix and necrotic chondrocytes, reduced synthesis and/or reduced of extracellular matrix and swelling of cell organelles such as mitochondria.The results of this study confirm our previously reported finding that quinolone-induced arthropathy probably is caued by a reduction of functionally available magnesium (ionized Mg2+ in cartilage. Furthermore, they provide a basis for aimed studies with human cartilage samples from quinolone-treated patients which might be available postmortal or after hip replacement surgery

  2. DNA Gyrase Is the Target for the Quinolone Drug Ciprofloxacin in Arabidopsis thaliana *

    OpenAIRE

    Evans-Roberts, Katherine M.; Mitchenall, Lesley A.; Wall, Melisa K.; Leroux, Julie; Mylne, Joshua S; Maxwell, Anthony

    2015-01-01

    The Arabidopsis thaliana genome contains four genes that were originally annotated as potentially encoding DNA gyrase: ATGYRA, ATGYRB1, ATGYRB2, and ATGYRB3. Although we subsequently showed that ATGYRB3 does not encode a gyrase subunit, the other three genes potentially encode subunits of a plant gyrase. We also showed evidence for the existence of supercoiling activity in A. thaliana and that the plant is sensitive to quinolone and aminocoumarin antibiotics, compounds that target DNA gyrase ...

  3. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil

    OpenAIRE

    Bruno Rocha Pribul; Marcia Lima Festivo; Miliane Moreira Soares de Souza; Dalia dos Prazeres Rodrigues

    2016-01-01

    Abstract Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n = 62) and human (n = 67) food were evaluated between 2009 and 2013. These isola...

  4. Use of in vitro topoisomerase II assays for studying quinolone antibacterial agents.

    OpenAIRE

    Barrett, J F; Gootz, T D; McGuirk, P R; C.A. Farrell; Sokolowski, S A

    1989-01-01

    Several quinolones and antitumor compounds were tested as inhibitors of purified calf thymus topoisomerase II in unknotting, catenation, radiolabeled DNA cleavage, and quantitative nonradiolabeled cleavage assays. The antitumor agents VP-16 (demethylepipodophyllotoxin ethylio-beta-D-glucoside) and ellipticine demonstrated drug-enhanced topoisomerase II DNA cleavage (the concentration of drug that induced 50% of the maximal DNA cleavage in the test system [CC50]) at levels of less than or equa...

  5. Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

    International Nuclear Information System (INIS)

    In search for new cytotoxic agents with improved anticancer profile, some new halogen-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7). The most potent compounds, as concluded from the in vitro anticancer screening, were selected to be evaluated again for their in vitro anticancer activity in combination with radiation. Also, the newly synthesized compounds were docked in the active site of the carbonic anhydrase enzyme

  6. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew;

    2015-01-01

    .6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using......Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of “stealth” design principals...... is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential −56 ± 5...

  7. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof

    2016-01-01

    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  8. In-silico Design, Synthesis, Anti-inflammatory and Anticancer Evaluation of Pyrazoline Analogues of Vanillin

    Directory of Open Access Journals (Sweden)

    M. J. Neethu

    2014-04-01

    Full Text Available A series of novel pyrazoline derivatives of vanillin were synthesized. The hydroxyl group in vanillin was masked by converting into methyl vanillin. The methyl vanillin was allowed to condense with different acetophenone derivatives gave chalcone derivatives and finally cyclized with thiosemicarbazide to form the pyrazoline derivatives of vanillin. Docking studies were carried out against anti-inflammatory cyclooxygenase receptor and anticancer farnesyl transferase receptor. Majority of the synthesized compounds showed good fitting with the active site of all the docked targets. The synthesized compounds had shown significant anti inflammatory and anticancer activities.

  9. 1,2-Substituted 4-(1H-Quinolones: Synthesis, Antimalarial and Antitrypanosomal Activities in Vitro

    Directory of Open Access Journals (Sweden)

    Abraham Wube

    2014-09-01

    Full Text Available A diverse array of 4-(1H-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC50 value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC50 value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities.

  10. Synthesis of Unnatural 2-Substituted Quinolones and 1,3-Diketones by a Member of Type III Polyketide Synthases from Huperzia serrata.

    Science.gov (United States)

    Wang, Juan; Wang, Xiao-Hui; Liu, Xiao; Li, Jun; Shi, Xiao-Ping; Song, Yue-Lin; Zeng, Ke-Wu; Zhang, Le; Tu, Peng-Fei; Shi, She-Po

    2016-08-01

    A curcuminoids, benzalacetone-, and quinolone-producing type III polyketide synthase (HsPKS3) from Huperzia serrata uniquely catalyzes the formation of unnatural 2-substituted quinolones and 1,3-diketones via head-to-head condensation of two completely different substrates. The broad range of substrate tolerance of HsPKS3 facilitates accessing structurally diverse 2-substituted quinolones and 1,3-diketones. PMID:27399835

  11. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil

    Science.gov (United States)

    Pribul, Bruno Rocha; Festivo, Marcia Lima; de Souza, Miliane Moreira Soares; dos Prazeres Rodrigues, Dalia

    2016-01-01

    Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n = 62) and human (n = 67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6′)-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6′)-Ib. The conserved integron region was detected in 67 isolates as variable regions, from ±600 to >1000 pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored. PMID:26887245

  12. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li; Luo, Qun-Li; Wang, En-Bo

    2013-02-01

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]rad H2O (1), [M(norfH)(bpdc)]rad H2O (M=Cd (2) and Mn (3)), [Mn2(cfH)(odpa)(H2O)3]rad 0.5H2O (4), [Co2(norfH)(bpta)(μ2-H2O)(H2O)2]rad H2O (5) and [Co3(saraH)2(Hbpta)2(H2O)4]rad 9H2O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4'-biphenyldicarboxylate, odpa=4,4'-oxydiphthalate, bpta=3,3',4,4'-biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {M(COO)}nn+ chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed.

  13. 喹诺酮类药物的研究进展%Research Progress of Quinolones

    Institute of Scientific and Technical Information of China (English)

    田秋月

    2014-01-01

    喹诺酮类药物是一类人工合成的抗菌药物,目前广泛应用于临床抗感染治疗中,具有较强的抗菌活性。本文主要从喹诺酮类药物的作用机制、临床应用、不良反应及耐药机制等方面进行分析和整理,综述其研究进展并对其未来的研究方向提出了建议,希望为今后喹诺酮药物的研究提供一定的参考依据。%Quinolones are a group of synthetic antibacteril drugs with strong antibacterial activity which have a broad range of clinic applications in recent years. In this article, research progress of quinolones was analyzed and summarized from the aspects of action mechanism, clinical application, adverse reactions and drug resistance mechanism, and the future research direction of quinolones was proposed.

  14. [Classification and prevalence of plasmid-mediated quinolone resistance qnr genes in China--A review].

    Science.gov (United States)

    Yan, Lei; Xu, Hai

    2016-02-01

    Quinolone antibacterial drugs, developing from the treatment of urinary tract infection in early time and now from the treatment of intestinal infection and respiratory infection, have been widely used in clinical, animal husbandry and aquaculture. Bacteria gradually become resistant to them and resistance mechanism is more and more complicated. Quinolone resistance mechanism is mainly divided into chromosome mediated resistance and plasmid mediated resistance, the latter plays an important role in spreading of antibiotic resistance. In 1998, plasmid mediated quinolone resistance mechanism was reported for the first time, namely the qnr gene mediated fluoroquinolone resistance mechanism. qnr genes can spread rapidly in different bacteria, which causes the infection difficult to control, makes the nosocomial infection popular in a wide range. In addition, qnr genes are usually associated with β-lactamase resistance gene. They exist in complex integron and integrate with the other varieties of resistance genes, which narrows the space of clinical medicine choose or drug combinations use to treat related bacterial infection and brings us a serious challenge. In this review, we provide a detailed overview for the historical discovery, classification, the resistance mechanisms of qnr genes, and the prevalence of those genes in China. PMID:27373065

  15. Study on Synthesis and Anticancer Activities of New Norlignans Derivatives%新型脱碳木脂素类化合物合成方法与肿瘤抑制活性研究

    Institute of Scientific and Technical Information of China (English)

    向建南; 刘开建; 李君姊; 梁志武

    2012-01-01

    利用Mn (Ⅱ)/Co(Ⅱ)/PhP (O) HOR/O2新催化体系合成了一系列新型脱碳木脂素类化合物(2a~2g),并采用MTT比色实验法,研究了所合成化合物体外抗肿瘤抑制活性.分别对人乳腺癌细胞(MCF-7),人肝癌细胞(Bel-7402),人肺癌(A549)和人子宫颈癌细胞(Hela)进行检测.结果表明:化合物2a~2g对4种癌细胞均有较强的抑制作用,尤其是对人肝癌细胞Bel-7402的抑制效果明显,其中化合物2b显示出比相同条件下紫杉醇更好地抗癌抑制活性(IC50:18.9μg/mL),说明所合成的芳基烯二聚化合物2b具有更好的应用前景.%In this study, we have synthesized a series of new norlignan compounds 2a~2g and evaluated their anticancer activities with MTT assay by using human hepaioma Bel-7402 cells, human breast ade-nocarcinoma MCF-7 cells, human lung carcinoma A549 cells and human cervical carcinoma HeLa cells. It has been shown that the products (2a-2g) exhibit higher cytotoxicity to cells, and especially, product 2b treated with Bel-7402 cells shows a lower cytotoxicity (IC50: 18. 9μg/mL) than free paclitaxel.

  16. Triterpenoids of Marine Origin as Anti-Cancer Agents

    OpenAIRE

    Yong-Xin Li; Himaya, S.W.A.; Se-Kwon Kim

    2013-01-01

    Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry ...

  17. MEDICINAL PLANTS WITH POTENTIAL ANTICANCER ACTIVITIES: A REVIEW

    OpenAIRE

    Narah Merina; Kalita Jogen Chandra; Kotoky Jibon

    2012-01-01

    Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against can...

  18. Detection of quinolones in commercial eggs obtained from farms in the Espaíllat Province in the Dominican Republic.

    Science.gov (United States)

    Moscoso, S; de los Santos, F Solís; Andino, A G; Diaz-Sanchez, Sandra; Hanning, I

    2015-01-01

    Previously, we reported the use of quinolones in broiler chickens resulted in residues in retail poultry meat obtained from nine districts in the Santiago Province of the Dominican Republic. Residues in poultry products are a concern due to consumer allergies and the potential to develop antibiotic-resistant bacteria. Given the use of quinolones in poultry production and our previous findings in poultry meat, the objective of this study was to evaluate the presence of quinolone residues in eggs. Samples were collected from 48 different farms located in three of the four municipalities (Moca, Cayetano Germosén, and Jamao) of the Espaíllat Province. Each farm was sampled three times between July and September for a total of 144 samples. Samples were evaluated qualitatively and quantitatively for quinolone residues using the Equinox test. Operation systems (cage or floor), seasonality, and location were considered along with egg-producer sizes that were defined as small scale, 60,000 eggs per day. From small-, medium-, and large-scale producers, 69, 50, and 40% of samples were positive for quinolone residues, respectively. A greater number of samples were positive (61%) in floor-laying hen producers compared with those using cages (40%). In the Jamao municipality, 67% of the samples were positive compared with Moca and Cayetano Germosén, where 56 and 25% of samples were positive, respectively. Sampling time had an effect on percent positives: samples collected in July, August, and September were 71, 19, and 63% positive, respectively. Overall, 51% of the samples obtained from eggs produced in the province of Espaíllat were positive for quinolone residues at levels higher than the maximum limits for edible tissue established by the regulatory agencies, including the European Union and U.S. Department of Agriculture. The results obtained from this research confirmed the presence of quinolone residue in eggs, which may present a health risk to some consumers. PMID

  19. Bacteriocins as potential anticancer agents

    OpenAIRE

    Sukhraj eKaur; Sumanpreet eKaur

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  20. Bacteriocins as Potential Anticancer Agents

    OpenAIRE

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  1. Novel Anticancer Agents from Ascidiacea

    OpenAIRE

    Vervoort, Hélène C.

    1999-01-01

    This thesis presents an effort to contribute to the discovery and development of struc­turally and mechanistically novel anticancer drugs. In order to reach this goal it focusses on the biologically active secondary metabolites of marine invertebrates of the class As­cidiacea (phylum Chordata, subphylum Urochordata (Tunicata), class Ascidacea). Three distinct areas of research were combined. The first part concerns the discovery of two novel, naturally occurring didemnin depsipeptide...

  2. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    OpenAIRE

    Gomes, Nelson G. M.; Ramesh Dasari; Sunena Chandra; Robert Kiss; Alexander Kornienko

    2016-01-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current revi...

  3. Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds

    OpenAIRE

    Kowol, Christian R.; Heffeter, Petra; Miklos, Walter; Gille, Lars; Trondl, Robert; Cappellacci, Loredana; Berger, Walter; Keppler, Bernhard K.

    2011-01-01

    Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-amino-pyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone a...

  4. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    OpenAIRE

    Sumitra Chanda; Krunal Nagani

    2013-01-01

    Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for...

  5. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    Directory of Open Access Journals (Sweden)

    Sumitra Chanda

    2013-07-01

    Full Text Available Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for estimating anticancer properties of natural products from medicinal plants. In this review, 50 anticancer medicinal plants of Indian origin belonging to 35 families are reported along with detailed information regarding part used, extract used, type of the model used, types of tested cancer cell lines, etc. These plants continue to be used against various types of tumours such as sarcoma, lymphoma, carcinoma and leukemia. All these plants are potential candidates for in vivo studies since they are showing good in vitro anticancer activity.

  6. SYNTHESIS OF NEW TWO DERIVATIVES OF 6-MERCAPTOPURINE (6MP 6-[5-PYRIDINE-4-YL- 1, 2, 3, 4-OXADIAZOLE-2-YLDITHIOL]-9H-PURINE (38 AND 9H-PURINE-6-YL-BENYLDITHIOCARBAMATE (45 WITH CYTOTOXICITY RESULTS FROM THE NATIONAL CANCER INSTITUTE'S ANTICANCER DRUG SCREEN

    Directory of Open Access Journals (Sweden)

    Mohammed Hassan Mohammed et al

    2012-08-01

    Full Text Available 6-[(5-pyridine-yl-1, 2, 3, 4-oxadiazole-2-yldithiol]-9H-purine (38 and 9H-purine-6yl-benzyldithiocarbamate (45 are synthesized as possible prodrugs for 6-mercaptopurine(6-MP. The generation of the compounds 38, 42, 45 and 48 were accomplished following multistep reaction procedures. The reaction and purity of the products were checked by TLC, the structure of the final compounds and their intermediates were confirmed by their melting points, infra red spectroscopy and whether differences elemental microanalysis. To determine exist among in sensitivity different tissue types toward treatment with 38 and 45. The cytotoxicity of the two compounds and their intermediates were confirmed by their melting points, infra red spectroscopy and elemental microanalysis. The cytotoxicity of two derivatives (38 and 45 was assessed in National Cancer Institute's anticancer screening program, and the results were compared with the cytotoxicity of 6-MP obtained in the same screen. The results show that the compound 38 and 45 were more cytotoxic than 6-MP. Additionally the prodrugs are less effective against leukemia cell line than 6-MP. Both derivatives exhibited high growth-inhibitory activities in renal cell line. However, compound 45 is more cytotoxic than 38 against ovarian cell line.

  7. Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents.

    Science.gov (United States)

    Tiwari, Shailee V; Seijas, Julio A; Vazquez-Tato, M Pilar; Sarkate, Aniket P; Lokwani, Deepak K; Nikalje, Anna Pratima G

    2016-01-01

    Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI50 value of 32.7 μM, 55.3 μM, 34.3 μM, 28.9 μM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like properties. PMID:27483213

  8. Looking for the new preparations for antibacterial therapy III. New antimicrobial agents from the quinolones group in clinical trials.

    Science.gov (United States)

    Karpiuk, Izabela; Tyski, Stefan

    2013-01-01

    There is an essential need for searching for the new compounds effective in the treatment of infections caused by multidrug-resistant bacteria. This paper is the third part of a series associated with the exploration of new antibacterial agents and it discusses the compounds belonging to the group of quinolones and substances possessing a hybrid structure composed of the quinolone molecule and other compounds. Eleven new substances at the stage of clinical trials are presented. Three of them belong to the group of non-fluorinated quinolone (nemonoxacin, ozenoxacin and KRP-AM 1977X), while six are the quinolones containing fluorine atom at 6 position of the carbon atom in the quinoline ring (zabofloxacin, finafloxacin, delafloxacin, JNJ-Q2, WCK771 and KPI-10). The remaining two compounds possess a hybrid construction composed of the quinolone structure and other molecules (cadazolid and CBR-2092). There is a chance in the near future, that the presented compounds can extend the range of existing antibacterial drugs and provide an alternative to currently available medicinal products.

  9. [Occurrence of quinolone and sulfonamide antibiotics in swine and cattle manures from large-scale feeding operations of Guangdong Province].

    Science.gov (United States)

    Tai, Yi-Ping; Luo, Xiao-Dong; Mo, Ce-Hui; Li, Yan-Wen; Wu, Xiao-Lian; Liu, Xing-Yue

    2011-04-01

    The occurrence and distribution of four quinolones and four sulfonamides in swine and cattle feces sampled from twenty large-scale feeding operations in different areas of Guangdong province were detected using solid phase extraction (SPE) and high performance liquid chromatography (HPLC). Quinolone and sulfonamide compounds were observed in all pig dung samples. Their total concentrations ranged from 24.5 microg/kg to 1516.2 microg/kg (F. W.) with an average of 581.0 microg/kg and ranged from 1925.9-13399.5 microg/kg with an average of 4403.9 microg/kg respectively. The dominant compounds in pig feces were ciprofloxacin and enrofloxacin for quinolones and sulfamerazine and sulfamethoxazole for sulfonamides. Quinolone compounds which dominated with norfloxacin and ciprofloxacin were also observed in all cattle dung samples, its total concentrations ranged from 73.2 microg/kg to 1328.0 microg/kg which averaged 572.9 microg/kg. While the positive rates of sulfonamide compounds detected in cattle dung samples were above 90%, predominated by sulfamethoxazole and sulfamerazine. Concentration and distribution of both quinolone and sulfonamide compounds in swine and cattle dungs of different feeding operations varied greatly. Relatively high concentrations of the two kinds of antibiotics were found in both swine and cattle dungs from Guangzhou area, while sulfameter and sulfamethazine in cattle dungs from Foshan and Shenzhen areas were below the limit of detection. PMID:21717768

  10. In Vitro Activity of the Quinolone WCK 771 against Recent U.S. Hospital and Community-Acquired Staphylococcus aureus Pathogens with Various Resistance Types▿

    OpenAIRE

    Bhagwat, Sachin S.; McGhee, Pamela; Kosowska-Shick, Klaudia; Patel, Mahesh V.; Appelbaum, Peter C.

    2008-01-01

    WCK 771 demonstrated MIC50 and MIC90s of 0.03 and 1 μg/ml, respectively, against 297 recent U.S. community-acquired and hospital strains of Staphylococcus aureus, irrespective of quinolone or glycopeptide resistance. Against quinolone-resistant strains, MIC90s of WCK 771 and moxifloxacin were 1 and 16 μg/ml, respectively.

  11. Deep sea as a source of novel-anticancer drugs

    OpenAIRE

    Russo, Patrizia; Del Bufalo, Alessandra; Fini, Massimo

    2015-01-01

    The deep-sea habitat is a source of very potent marine-derived agents that may inhibit the growth of human cancer cells “in vitro” and “in vivo”. Salinosporamide-A, Marizomib, by Salinispora species is a proteasome inhibitor with promising anticancer activity (Phase I/II trials). Different deep-sea-derived drugs are under preclinical evaluation. Cancer is a complex disease that may be represented by network medicine. A simple consequence is the change of the concept of target entity from a si...

  12. USE OF QUINOLONES IN BULL SEMEN EXTENDERS TO REDUCE SPERM DEOXYRIBONUCLEIC ACID DAMAGE

    Directory of Open Access Journals (Sweden)

    Clara Gonzalez-Marin

    2012-01-01

    Full Text Available Cryopreserved sperm samples from Holstein bulls (n = 20 were examined for bacterial presence and Sperm DNA Fragmentation (SDF dynamics. SDF was assessed after thawing (T0 and at 4, 24 and 48 h of incubation (37°C and the rate of SDF (r-SDF, as an estimator of the DNA degradation over time, was calculated. Two groups of bulls were identified based on the presence or absence of bacteria: One group (n = 10 had a readily detectable bacterial presence, while the other group (n = 10 had an undetectable bacterial presence. Differences in the SDF at T0 were not observed between these two groups. However, statistically different results were found after 24 h of incubation at 37°C (Kaplan-Meier estimator; Log-Rank Matel-Cox, p-1 of ciprofloxacin at T0. Differences in the r-SDF (p>0.05 were not detected between the control and the quinolone treated sample for those samples without bacteria. However, differences (p<0.000 in SDF were observed for quinolone treated samples that previously presented bacteria. Incubation of sealed straws showed that bacterial contamination occurred prior to cryopreservation. These results call attention to three points: (1 sperm samples were in contact with bacteria before cryopreservation; (2 the r-SDF can be directly correlated with bacterial presence but this effect remains cryptic after thawing and (3 the r-SDF can be reduced by treating the semen samples with an adequate antibiotic such as quinolones, a finding not previously reported in the scientific literature, but important in terms of reproduction.

  13. In-silico Design, Synthesis, Anti-inflammatory and Anticancer Evaluation of Pyrazoline Analogues of Vanillin

    OpenAIRE

    M. J. Neethu; Shakkeela Yusuf

    2014-01-01

    A series of novel pyrazoline derivatives of vanillin were synthesized. The hydroxyl group in vanillin was masked by converting into methyl vanillin. The methyl vanillin was allowed to condense with different acetophenone derivatives gave chalcone derivatives and finally cyclized with thiosemicarbazide to form the pyrazoline derivatives of vanillin. Docking studies were carried out against anti-inflammatory cyclooxygenase receptor and anticancer farnesyl transferase receptor. Majority of the s...

  14. The measurement of a new antimicrobial quinolone in hair as an index of drug exposure.

    OpenAIRE

    Uematsu, T.; Nakano, M; Akiyama, H.; Nakashima, M.

    1993-01-01

    1. Scalp hair samples were obtained at 1 month intervals up to 5 months from healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, OPC-17116. 2. Hair was sectioned into 1 cm lengths from the scalp end. Corresponding portions from five pieces of hair were dissolved in 1 N NaOH and assayed for OPC-17116 by h.p.l.c. 3. In all subjects taking a single dose (400 mg, n = 5) or repeated doses (400 mg day-1, twice daily, for 6.5 days, n = 6), the drug was detected...

  15. Theobroma cacao: Review of the Extraction, Isolation, and Bioassay of Its Potential Anti-cancer Compounds.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Hin, Taufiq Yap Yun; Hamid, Roslida Abdul; Kasran, Rosmin

    2016-02-01

    Plants have been a good source of therapeutic agents for thousands of years; an impressive number of modern drugs used for treating human diseases are derived from natural sources. The Theobroma cacao tree, or cocoa, has recently garnered increasing attention and become the subject of research due to its antioxidant properties, which are related to potential anti-cancer effects. In the past few years, identifying and developing active compounds or extracts from the cocoa bean that might exert anti-cancer effects have become an important area of health- and biomedicine-related research. This review provides an updated overview of T. cacao in terms of its potential anti-cancer compounds and their extraction, in vitro bioassay, purification, and identification. This article also discusses the advantages and disadvantages of the techniques described and reviews the processes for future perspectives of analytical methods from the viewpoint of anti-cancer compound discovery. PMID:27019680

  16. Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone

    Directory of Open Access Journals (Sweden)

    Xuejing Lin

    2015-05-01

    Full Text Available Costunolide (CE and dehydrocostuslactone (DE are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.

  17. Molecular epidemiological survey on quinolone resistance genotype and phenotype of Escherichia coli in septicemic broilers in Hebei, China.

    Science.gov (United States)

    Xie, Rong; Huo, Shuying; Li, Yurong; Chen, Ligong; Zhang, Feiyan; Wu, Xianjun

    2014-02-01

    In this study, the quinolone-resistant determining region (QRDR) of gyrA of Escherichia coli and plasmid-mediated quinolone resistance (PMQR) genes, qnr(qnrA, qnrB, and qnrS), and aac(6 ')-Ib-cr were detected, sequenced, and analyzed. In addition, antimicrobial susceptibility tests (using the Kirby-Bauer disc diffusion method) were performed for all 111 E. coli isolates from septicemic broilers in Hebei, China. The results show that the resistance rates were as follows: ofloxacin 99.10%, ciprofloxacin 93.69%, levofloxacin 91.89%, norfloxacin 90.09%, and gatifloxacin 76.58%. Of the PMQR genes examined, aac(6 ')-Ib-cr (36.04%) was the most frequently identified gene in all isolates, followed by qnrS (8.11%), qnrB (0.90%), and qnrA (0%). Of the QRDR examined in the 40 phenotypic quinolone-resistant isolates, compared with the gyrA(+) gene of E. coli K-12, 4 amino acid exchanges were found, namely Ser-83→Asp, Asp-87→Asn, Asp-87→Tyr, and Asp-87→Ala, and all 40 isolates had 1 or 2 exchanges in QRDR. It was concluded that quinolone-resistance in E. coli remains a serious problem in Hebei, China. Therefore, there is considerable local surveillance of quinolone resistance. Plasmid-mediated quinolone resistance of the qnr type remains rare in Hebei, China, and mutation in QRDR may be the main problem.

  18. First Streptococcus agalactiae Isolates Highly Resistant to Quinolones, with Point Mutations in gyrA and parC

    OpenAIRE

    Kawamura, Yoshiaki; Fujiwara, Hiromitsu; Mishima, Noriko; Tanaka, Yuko; Tanimoto, Ayako; Ikawa,Shiro; Itoh, Youko; EZAKI, Takayuki

    2003-01-01

    Three isolates of Streptococcus agalactiae highly resistant to multiple fluoroquinolones were isolated in Japan. Compared with susceptible strains of S. agalactiae, these quinolone-resistant strains had double point mutations within the quinolone resistance-determining regions of gyrA and parC; Ser-81 was changed to Leu (TCA → TTA) in the amino acid sequence deduced from gyrA, and Ser-79 was changed to Phe (TCC → TTC) in the amino acid sequence deduced from parC. Comparative sequence analysis...

  19. Ganoderma: insights into anticancer effects.

    Science.gov (United States)

    Kladar, Nebojša V; Gavarić, Neda S; Božin, Biljana N

    2016-09-01

    The genus Ganoderma includes about 80 species growing on cut or rotten trees. The most commonly used species is Ganoderma ludicum. Biomolecules responsible for the health benefits of Ganoderma are polysaccharides with an immunostimulative effect and triterpenes with a cytotoxic action. For more than 2000 years, it has been used traditionally in the treatment of various pathological conditions and recently, its immunoregulatory, antiviral, antibacterial, antioxidant, hepatoprotective, and anticancer potential has been confirmed. A wide range of Ganoderma extracts and preparations arrest the cell cycle in different phases and consequently inhibit the growth of various types of cancer cells. Extracts containing polysaccharides stimulate immunological reactions through the production of various cytokines and mobilization of immune system cells. In-vivo studies have confirmed the anticancer potential and the antimetastatic effects of compounds originating from Ganoderma. There is also evidence for the chemopreventive action of Ganoderma extracts in bladder, prostate, liver, and breast cancer. The results of clinical studies suggest the combined use of G. lucidum with conventional chemotherapy/radiotherapy, but the methodology and the results of these studies are being questioned. Therefore, a constant need for new clinical trials exists. PMID:26317382

  20. Synthesis of four binuclear copper(II) complexes: Structure, anticancer properties and anticancer mechanism.

    Science.gov (United States)

    Qi, Jinxu; Liang, Shichu; Gou, Yi; Zhang, Zhenlei; Zhou, Zuping; Yang, Feng; Liang, Hong

    2015-01-01

    Copper (Cu) compounds are a promising candidate for next generation metal anticancer drugs and have been extensively studied. Therefore, four binuclear copper(II) compounds derived from Schiff base thiosemicarbazones (L1-L4), namely [CuCl(L1)]2 (C1), [CuNO3(L2)]2 (C2), [Cu(NCS) (L3)]2 (C3) and [Cu(CH3COO) (L4)]2 (C4) were synthesized and characterized. Four of these compounds showed very high cytotoxicity to cancer cell lines in vitro. These Cu(II) compounds strongly promoted the apoptosis of BEL-7404 cells. The formation of reactive oxygen species (ROS), change in mitochondrial membrane potential and western blot analysis revealed that Cu compounds could induce cancer cell apoptosis through the intrinsic ROS-mediated mitochondrial pathway accompanied by the regulation of Bcl-2 family proteins. PMID:25899339

  1. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  2. Novel Marine Compounds: Anticancer or Genotoxic?

    Directory of Open Access Journals (Sweden)

    Arif Jamal M.

    2004-01-01

    Full Text Available In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

  3. 喹诺酮抗HIV活性及其构效关系的研究进展%Advances of Quinolones as Potent HIV Inhibitors and Their Structure-activity Relationships

    Institute of Scientific and Technical Information of China (English)

    冯连顺; 王健; 刘明亮; 吕凯; 郭慧元

    2011-01-01

    The quinolone is one of the important scaffolds to find new anti-HIV drugs in recent years. Many series of derivatives were designed and synthesized through structural modification, and some of them were found to be promising HIV integrase inhibitors, reverse transcriptase inhibitors or dual inhibitors of reverse transcriptase and integrase. It is encouraging that elvitegravir as an integrase inhibitor, the first quinolone anti-HIV drug, will be approved by US FDA for the treatment of AIDS. This article describes the research advances of quinolones as potent anti-HIV agents, their structure-activity relationships and related action mechanisms.%喹诺酮是近年来寻找抗HIV新药的重要结构骨架之一.通过结构修饰,可从中筛选出若干有希望的整合酶抑制剂、逆转录酶抑制剂以及双重(逆转录酶+整合酶)抑制剂.尤其是整合酶抑制剂elvitegravir即将上市,引起对抗HIV喹诺酮研发的关注.本文按喹诺酮的结构特征,从2-喹诺酮、4-喹诺酮、β-二酮酸和杂合体着手,综述了近年来这类化合物在抗HIV活性及其构效关系、作用机制等方面的研究进展.

  4. In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses.

    Science.gov (United States)

    Liebscher, G; Vanchangiri, K; Mueller, Th; Feige, K; Cavalleri, J-M V; Paschke, R

    2016-02-25

    Betulinic acid, a pentacyclic triterpene, and its derivatives are promising compounds for cancer treatment in humans. Melanoma is not only a problem for humans but also for grey horses as they have a high potential of developing melanoma lesions coupled to the mutation causing their phenotype. Current chemotherapeutic treatment carries the risk of adverse health effects for the horse owner or the treating veterinarian by exposure to antineoplastic compounds. Most treatments have low prospects for systemic tumor regression. Thus, a new therapy is needed. In this in vitro study, Betulinic acid and its two derivatives B10 and NVX-207, both with an improved water solubility compared to Betulinic acid, were tested on two equine melanoma cell lines (MelDuWi and MellJess/HoMelZh) and human melanoma (A375) cell line. We could demonstrate that all three compounds especially NVX-207 show high cytotoxicity on both equine melanoma cell lines. The treatment with these compounds lead to externalization of phosphatidylserines on the cell membrane (AnnexinV-staining), DNA-fragmentation (cell cycle analysis) and activation of initiator and effector caspases (Caspase assays). Our results indicate that the apoptosis is induced in the equine melanoma cells by all three compounds. Furthermore, we succeed in encapsulating the most active compound NVX-207 in 2-Hydroxyprolyl-β-cyclodextrine without a loss of its activity. This formulation can be used as a promising antitumor agent for treating grey horse melanoma. In a first tolerability evaluation in vivo the formulation was administered every one week for 19 consecutive weeks and well tolerated in two adult melanoma affected horses. PMID:26772157

  5. Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A

    Directory of Open Access Journals (Sweden)

    Sylvie eBaucheron

    2014-01-01

    Full Text Available Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e. in gyrA, gyrB, or parC correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications.

  6. Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens

    Directory of Open Access Journals (Sweden)

    Orhiosefe Omigie

    2009-08-01

    Full Text Available Orhiosefe Omigie, Lawrence Okoror, Patience Umolu, Gladys IkuuhDepartment of Microbiology, Ambrose Alli University, Ekpoma, NigeriaAbstract: A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%, Escherichia coli (26.3%, and Proteus spp. (17.1%. Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase, Staphylococcus aureus (9.8%, and E. coli (9.7%. The highest potency was exhibited by ciprofloxacin (91.2%, levofloxacin (89.2%, and moxifloxacin (85.1%, while there were high rates of resistance to nalidixic acid (51.7% and pefloxacin (29.0%. Coliforms, particularly E. coli (>45%, remain the most prevalent causative agents of UTI while females within the age range of 20–50 years were most vulnerable to UTI.Keywords: UTI, microorganisms, antibiotics, resistance

  7. Deriving Derivatives

    OpenAIRE

    Soklakov, Andrei N.

    2013-01-01

    Quantitative Structuring is a rigorous framework for the design of financial products. We show how it incorporates traditional investment ideas while supporting a more accurate expression of clients' views on the market. We briefly touch upon adjacent topics regarding the safety of financial derivatives and the role of pricing models in product design.

  8. Bacteriocins as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sukhraj eKaur

    2015-11-01

    Full Text Available Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity towards cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  9. Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

    Directory of Open Access Journals (Sweden)

    Mingliang Chen

    2015-06-01

    Full Text Available Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84% in 1965-1973 to serogroup A CC1 (58% in 1974-1985, then to serogroup C or B CC4821 (62% in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37 in 2005-2013 (p < 0.001. Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31 were assigned to either CC4821 (n = 20 or CC5 (n = 7. The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31 of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31 of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15 among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available

  10. Design, Synthesis, Characterization and Anticancer Prope rties of Novel 2-Chloro- N -(Aryl Substituted Acetamide Derivatives of 5-[2-(4- Methoxyphenyl Pyridin-3-yl]-1, 3, 4-Oxadiazole-2-Thiol

    Directory of Open Access Journals (Sweden)

    Adimule Vinayak

    2014-12-01

    Full Text Available In this linear synthesis, novel different 2-chloro N-aryl substitutedacetamide derivatives of 5-[2-(4-methoxyphenyl pyridin-3-yl]-1, 3, 4-oxadiazole-2-thiol have been synthesized and screened for their cytotoxicity on PANC-1, HepG2and MCF7cell lines and obtained the IC50and CC50values.All the synthesized compounds were characterized by LCMS, IR, 1H and 13C (proton and Carbon 13 spectroscopies and elemental analysis. These compounds were evaluated for invitroanticancer activity on three different human leukemic cell lines, namely PANC-1,HepG2and MCF7.In total five compounds were synthesized and studied for their MTT assay. Among five synthesized novel compounds, the compound N-[5-(4-Methoxy-phenyl-pyridin-2-yl]-2-{5-[2-(4-methoxy-phenyl-pyridin-3-yl][1,3,4]oxadiazol-2 ylsulfanyl}-acetamide6eis highly cytotoxic on PANC-1and HepG2cell lines having IC50of 4.6μM and 2.2μM respectively whereas the compound 6cis moderately cytotoxic on MCF7having IC5015.5μM respectively. Rest all the compounds showed less cytotoxicity on all the three cell lines as compared with the standard 5-FU.

  11. 一种黄酮衍生物的合成及其体外抗癌活性%Synthesis of a flavone derivative and evaluation of its in vitro anti-cancer activity

    Institute of Scientific and Technical Information of China (English)

    范攀越; 王江; 黄远; 张幸博

    2013-01-01

    以柚皮素为原料,通过对其结构进行修饰,合成了黄酮衍生物5-羟基-2-(4羟基苯基)-7-(2-吗啉基乙氧基)-4H-苯骈吡喃-4-酮;利用核磁共振、元素分析及质谱确认了产物的结构,利用MTT法测定了其对人肝癌细胞(HepG2)、7721以及QSG7701正常肝细胞株的抑制率.结果表明,同槲皮素相对照,合成的黄酮衍生物对肝癌细胞具有良好的抑制活性.%A flavone derivative, 5-hydroxyl-2-(4-hydroxyphenyl)-7-(2-morpholinoethoxy)-4H-chroxmen-4-one, was synthesized with naringenin as the raw material. The structure of as-synthesized product was characterized by nuclear magnetic resonance spectroscopy, elemental analysis and mass spectrometry. Moreover, the inhibition ratio of the synthesized product for human liver cells (HepG2) and SMMO7721 human hepatoma cell line as well as normal human fetal liver (QSG-7701) was tested with MTT method. Results show that as-synthesized compound has good inhibitory activity against the cells of liver canner.

  12. Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones(p-toluamidrazones) and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

    Institute of Scientific and Technical Information of China (English)

    BEKIRCAN Olcay; KAHVECI Bahittin; OZGUMUS Osman Birol

    2007-01-01

    Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones (p-toluamidrazones) 3a-3d,and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates.The structures of compounds 3 and 4 were established on the basis of elemental analyses,IR,1H NMR,13C NMR and UV data.Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d,4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193.However,compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923.The other compounds showed neither antifungal nor antibacterial activities.Compounds 3a,4a and 4b have been screened on three human tumor cell lines,breast cancer (MCF7),non small cell lung cancer (NCI-H460),and CNS cancer (SF-268) at the National Cancer Institute (NCI),USA,which were found to exhibit low antiproliferative activity.

  13. A Facile Solid Phase Synthesis of 2—Alkylthio—4(1H)—quinolones

    Institute of Scientific and Technical Information of China (English)

    TANG,Jing; WU,Ming-Guang; HUANG,Xian

    2003-01-01

    The resin-bound cyclic malonic acid ester 2 reacted with aryl isothiocyanate and alkyl halides to afford the key intermediate arylthioaminomethylene cyclic malonic ester resin 3.Subsequently,resin 3 proceeded thermal cyclizaiton giving the 2-alkylthio-4(1H)-quinolones in good yields and excellent purties.

  14. Studies on the antagonistic action between chloramphenicol and quinolones with presence of bovine serum albumin by fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Liu Baosheng, E-mail: lbs@hbu.edu.c [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China); Zhao Fengli; Xue Chunli; Wang Jing; Lu Yunkai [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China)

    2010-05-15

    Chloramphenicol (CHL) and quinolone drugs like ofloxacin (OFLX), lomefloxacin (LMX) and ciprofloxacin (CPFX) can all quench the fluorescence of bovine serum albumin (BSA) in the aqueous solution of pH=7.40. This quenching effect becomes more significant when CHL and quinolone drugs coexist. Based on this, further studies on the interactions between CHL and quinolone drugs using fluorescence spectrum are established. The results showed that the interaction between the drugs would increase the binding constant and binding stability of the drug and protein, thus reducing the amount of drugs transported to their targets. Therefore, free drug concentration at targets would decrease, reducing the efficacy of the drugs. It indicated that there exists antagonistic action between drugs. The results also showed that the quenching mechanism of BSA by the drugs is a static procedure. The number of binding sites is 1 in various systems. Due to the existence of the antagonistic action between drugs, the binding distance r is reduced. Studies utilizing synchronous spectra showed that the antagonistic action between the drugs would affect the conformation of BSA, making protein molecules extend and hydrophobic decrease. The order of antagonistic action between CHL and quinolone drugs is: CPFX>OFLX>LMX with presence of BSA.

  15. Progress in research on quinolone antibacterials%喹诺酮类抗菌药物研究新进展

    Institute of Scientific and Technical Information of China (English)

    蒋晓磊; 崔玉彬; 曹胜华

    2011-01-01

    This article has reviewed progress in research on quinolone antibacterials in recent years,which consisted of newly launched products, agents in clinical trials and future development of this kind of drugs. It focused on some clinical promising candidates. Among these drugs, delafloxacin would be the most potential candidate.Moreover it introduced new fields of the future development, including modifying side chain, quinolone-like compounds, antibacterial quinolone hybrids and anti-TB quinolone-drug conjugates.%本文简述了喹诺酮类药物近几年的研究进展,分为上市药物、临床试验药物和未来发展趋势三部分,对目前处于临床研究阶段的药物做了重点讲述,其中delafloxacin是最有希望的喹诺酮类候选药物,同时介绍了喹诺酮类抗菌药物的未来发展方向,即侧链修饰、喹诺酮类似物、喹诺酮杂合物和TB药物与喹诺酮扼合物.

  16. Rational use of quinolones antibiotics%合理应用喹诺酮类抗菌药物

    Institute of Scientific and Technical Information of China (English)

    宋惠珠

    2011-01-01

    目的 了解喹诺酮类抗菌药物的作用机制,不良反应及使用时的注意事项. 方法 对喹诺酮类抗菌药物在临床使用中的注意事项及所涉及的不良反应进行汇总. 结果 随着临床使用喹诺酮类抗菌药物的增加,药物的不良反应也随着上升,其不良反应发生率<2.0%,肾损害的发生率为0.9%~4.3%. 结论 在广泛应用喹诺酮类抗菌药物的同时,要更多地关注其安全性.%OBJECTIVE To understand the mechanism of quinolones, adverse reactions and precautions when using.METHODS The precautions of quinolones in clinical use and the adverse reactions involved were aggregated.RESULTS With the increased clinical use of quinolones, the incidence of adverse drug reactions was increased more than <2.0%. CONCLUSION In the widely use of quinolones antibiotics, their safety should be more concerned about.

  17. Quinolone- and ß-lactam-resistance in Escherichia coli from Danish and Italian broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne;

    Frederiksberg C, Denmark 2Dipartimento di Sanità Pubblica Veterinaria e Patologia Animale, Facoltà di Medicina Veterinaria, Università di Bologna, 40064 Ozzano Emilia (BO), Italy   The prevalence of quinolone- and ß-lactam-resistant E. coli was investigated among broiler flocks in Denmark and Italy. In Denmark...

  18. Detection of mutations in mtrR gene in quinolone resistant strains of N.gonorrhoeae isolated from India

    Directory of Open Access Journals (Sweden)

    S V Kulkarni

    2015-01-01

    Full Text Available Background and Objectives: Emergence of multi-drug resistant Neisseria gonorrhoeae resulting from new genetic mutation is a serious threat in controlling gonorrhea. This study was undertaken to identify and characterise mutations in the mtrR genes in N.gonorrhoeae isolates resistant to six different antibiotics in the quinolone group. Materials and Methods: The Minimum inhibitory concentrations (MIC of five quinolones for 64 N.gonorrhoeae isolates isolated during Jan 2007-Jun 2009 were determined by E-test method. Mutations in MtrR loci were examined by deoxyribonucleic acid (DNA sequencing. Results: The proportion of N.gonorrhoeae strains resistant to anti-microbials was 98.4% for norfloxacin and ofloxacin, 96.8% for enoxacin and ciprofloxacin, 95.3% for lomefloxacin. Thirty-one (48.4% strains showed mutation (single/multiple in mtrR gene. Ten different mutations were observed and Gly-45 → Asp, Tyr-105 → His being the most common observed mutation. Conclusion: This is the first report from India on quinolone resistance mutations in MtrRCDE efflux system in N.gonorrhoeae. In conclusion, the high level of resistance to quinolone and single or multiple mutations in mtrR gene could limit the drug choices for gonorrhoea.

  19. Analysis of the gyrA gene of clinical Yersinia ruckeri isolates with reduced susceptibility to quinolones.

    Science.gov (United States)

    Gibello, Alicia; Porrero, M Concepción; Blanco, M Mar; Vela, Ana I; Liébana, Pilar; Moreno, Miguel A; Fernández-Garayzábal, José F; Domínguez, Lucas

    2004-01-01

    Antimicrobial susceptibility of seven clinical strains of Yersinia ruckeri representative of those isolated between 1994 and 2002 from a fish farm with endemic enteric redmouth disease was studied. All isolates displayed indistinguishable pulsed-field gel electrophoresis restriction patterns, indicating that they represented a single strain. However, considering both inhibition zone diameters (IZD) and MICs, the isolates recovered in 2001-2002 formed a separate cluster with lower levels of susceptibility to all the quinolones tested, especially nalidixic acid (NA) and oxolinic acid (OA), compared with the isolates recovered between 1994 and 1998. Analysis of the PCR product of the quinolone resistance-determining region of the gyrA gene from clinical isolates of Y. ruckeri with reduced susceptibility to OA and NA revealed a single amino acid substitution, Ser-83 to Arg-83 (Escherichia coli numbering). Identical substitution was observed in induced OA-resistant mutant strains, which displayed IZD and MICs of quinolones similar to those of the clinical isolates of Y. ruckeri with reduced susceptibility to these antimicrobial agents. These data indicate in that for Y. ruckeri, the substitution of Ser by Arg at position 83 of the gyrA gene is associated with reduced susceptibility to quinolones.

  20. Quinolone resistance and ESBL/AmpC’s in commensal Escherichia coli in veal calves : prevalence and molecular characterization

    NARCIS (Netherlands)

    Hordijk, J.

    2013-01-01

    In this thesis the prevalence and molecular characteristics of resistance to (fluoro)quinolones and Extended Spectrum Cephalosporins (ESC) in veal calves were described using Escherichia coli as an indicator organism. Ciprofloxacin and nalidixic acid were used as indicator antimicrobials for quinolo

  1. Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization

    Directory of Open Access Journals (Sweden)

    Frank Thierry

    2011-08-01

    Full Text Available Abstract Background Cross-resistance to quinolones and beta-lactams is frequent in Enterobacteriaceae, due to the wide use of these antibiotics clinically and in the food industry. Prescription of one of these categories of antibiotic may consequently select for bacteria resistant to both categories. Genetic mechanisms of resistance may be secondary to a chromosomal mutation located in quinolone resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid acquisition. The insertion sequence ISCR1 is often associated with qnr and may favour its dissemination in Gram-negative bacteria. The aim of this study was to determine the genetic mechanism of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in the Central African Republic. Findings Among seventeen ESBL-producing Enterobacteriaceae isolated from urine, pus or stool between January 2003 and October 2005 in the Central African Republic, nine were resistant to ciprofloxacin (seven from community patients and two from hospitalized patients. The ESBL were previously characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid, norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these drugs were determined by disc diffusion and agar dilution methods, respectively. The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and amplicons, if any, were sent for sequencing. Quinolone resistance determining region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for mutation characterization. We found that all CTX-M-producing strains were resistant to the tested quinolones. All the isolates had the same nucleotide mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might favour dissemination of resistance to quinolone and perhaps other antibiotics among Enterobacteriaceae

  2. Plant antimicrobial peptides as potential anticancer agents.

    Science.gov (United States)

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E

    2015-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  3. A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots.

    Science.gov (United States)

    García-León, Guillermo; Hernández, Alvaro; Hernando-Amado, Sara; Alavi, Peyman; Berg, Gabriele; Martínez, José Luis

    2014-08-01

    Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It thus seems unlikely that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last few decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT. Our work shows that plant-produced flavonoids can bind to SmeT, releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicates that they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually downregulated unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned that this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots. Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and that colonization of plant roots is likely one original function of this efflux pump.

  4. (-)-Arctigenin as a lead compound for anticancer agent.

    Science.gov (United States)

    Chen, Gui-Rong; Li, Hong-Fu; Dou, De-Qiang; Xu, Yu-Bin; Jiang, Hong-Shuai; Li, Fu-Rui; Kang, Ting-Guo

    2013-01-01

    (-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6') and C (6″) and O-demethylation at CH3O-C (3'), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined. PMID:23962054

  5. [Impact on public health of quinolone resistance in animal-origin bacteria].

    Science.gov (United States)

    Orden Gutiérrez, J A; de la Fuente López, R

    2001-01-01

    Fluoroquinolones are one of the most useful classes of antimicrobial agents used in human and animal medicine today, both because of their spectrum and their physicochemical properties. The use of quinolones in animals is a matter of special concern because it could contribute to the acquisition of resistance in foodborn bacteria (such as Salmonella spp., Campylobacter spp. and Escherichia coli) and this, in turn, could lead to a reduction in the efficacy of such compounds in treating infections in humans. However, the causal relationship between the use of fluoroquinolones in veterinary medicine and the isolation of fluoroquinolone-resistant bacteria in humans has not been generally proven and, moreover, the use of fluoroquinolones in animals is only one of the many factors implicated in the resistance to these antimicrobials. Even so, the surveillance of fluoroquinolone resistance in bacteria isolated from animals and foods and the prudent use of these antimicrobials in animals should have the highest priority. PMID:11693069

  6. Occurrence of quinolone- and beta-lactam-resistant Escherichia coli in danish broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne;

    An increased concern for the possible transfer of resistant bacteria or mobile resistance elements from food animals to humans has resulted in rigorous legislation preventing i.e. practical use of fluoroquinolones in the Danish broiler industry (Olesen et al., 2004; Petersen et al., 2006...... and nalidixic acid resistances were detected in all flocks. The numbers of E. coli resistant to these drugs were higher in plates from parent flocks than in those from offspring flocks. A broiler parent flock without any history of quinolone usage tested positive for ciprofloxacin-resistant E. coli, although...... and mutations responsible for these types of resistance. References DANMAP 2005. 2006. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. Danish Veterinary Laboratory, Copenhagen, Denmark, ISSN 1600-2032. Olesen, I., H. Hasman...

  7. Resistance patterns to beta-lactams and quinolones in clinical isolates of bacteria from Cuban hospitals.

    Science.gov (United States)

    Gonzáles, I; Niebla, A; Vallin, C

    1995-01-01

    The resistance patterns to 26 beta-lactams and 8 quinolones of clinical isolates from Cuban hospitals were evaluated using the disk susceptibility test, according to the NCCLS guidelines (1992). The genera studied were Escherichia sp (320), Enterobacter sp (10), Klebsiella sp (90), Proteus sp (10), Pseudomonas sp (90), Serratia sp (20), and Staphylococcus sp (80). Higher resistance to beta-lactams was observed in the genera Pseudomonas, Escherichia and Klebsiella. For fluoroquinolones we found no significant resistance, with the exception of the genus Klebsiella. The most effective antibiotics were cephalosporins of the second and third generations, fluoroquinolones, and non-classical beta-lactams (cephamycins, moxalactam and monobactams). On the contrary, a pronounced resistance was found to penicillin, oxacillin, ticarcillin, ampicillin, methicillin, nalidixic acid and cinoxacin. These resistance patterns correspond to the high consumption of these antibiotics throughout the country.

  8. Capillary electrophoresis with electrochemiluminescence detection for the analysis of quinolone drugs and pharmacokinetics study

    Institute of Scientific and Technical Information of China (English)

    Yan Ming Liu; Jun Tao Cao; Hui Wang

    2008-01-01

    A novel method for the determination of two quinolone drugs norfloxacin (NOR) and levofloxacin (LVX) was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship (r ≥ 0.9991) between peak area and concentration of analytes was established over two orders of magnitude. The limits of detection (LOD, S/N = 3) in standard solution are 4.8 × 10-7 mol/L for NOR and 6.4 × 10-7 mol/L for LVX, respectively. The limits of quantitation (LOQ, S/N = 10) in real human urine samples are 1.2 × 10-6 mol/L for NOR and 1.4 × 10-6 mol/L for LVX, respectively. The present method was successfully applied to the determination of NOR and LVX in human urine and the study of pharmacokinetics of NOR.

  9. Determination of the stereoisomers in aqueous medium and serum and validation studies of racemic aminoalkanol derivatives of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, potential new anticancer drugs, by capillary electrophoresis.

    Science.gov (United States)

    Grodner, Błażej; Łukaszkiewicz, Jacek; Napiórkowska, Mariola

    2016-08-01

    A new method for the determination of the stereoisomers, in aqueous medium and serum, of the racemic aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which were found in earlier studies to be potential anticancer drugs, was developed and validated. The optimized conditions included 25 mM phosphate buffer adjusted to pH 2.5, containing γ-cyclodextrin at a concentration of 5% m/v, as background electrolyte, an applied voltage of +10 kV, and a temperature of 25°C. Separations were carried out using a fused-silica capillary. The developed method of determining the enantiomers of compounds I(S), I(R) and II(S), II(R) was characterized by the following parameters: a detection time within 10.8 min, a detection limit in the range of 141.2-141.7 ng/mL using the UV absorption detection at 200 nm. Good linearity (R(2) = 0.9989-0.9998) was achieved within the range of concentrations studied. A very good extraction yield of 95.4-99.7% was achieved, and recoveries were carried out from both aqueous solutions and matrix serum. The repeatability of the method for peak areas with an accuracy of the determined concentrations of the analytes in the range of 1.43-1.89%, and limits of quantitation in the range of 432.4-436.3 ng/mL were achieved. PMID:27421088

  10. Novel Marine Compounds: Anticancer or Genotoxic?

    OpenAIRE

    Arif, Jamal M.; Al-Hazzani, Amal A.; Muhammed Kunhi; Fahad Al-Khodairy

    2004-01-01

    In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft mode...

  11. Targeted anticancer therapy: overexpressed receptors and nanotechnology.

    Science.gov (United States)

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alrokayan, Salman A; Kumar, Sudhir

    2014-09-25

    Targeted delivery of anticancer drugs to cancer cells and tissues is a promising field due to its potential to spare unaffected cells and tissues, but it has been a major challenge to achieve success in these therapeutic approaches. Several innovative approaches to targeted drug delivery have been devised based on available knowledge in cancer biology and on technological advancements. To achieve the desired selectivity of drug delivery, nanotechnology has enabled researchers to design nanoparticles (NPs) to incorporate anticancer drugs and act as nanocarriers. Recently, many receptor molecules known to be overexpressed in cancer have been explored as docking sites for the targeting of anticancer drugs. In principle, anticancer drugs can be concentrated specifically in cancer cells and tissues by conjugating drug-containing nanocarriers with ligands against these receptors. Several mechanisms can be employed to induce triggered drug release in response to either endogenous trigger or exogenous trigger so that the anticancer drug is only released upon reaching and preferentially accumulating in the tumor tissue. This review focuses on overexpressed receptors exploited in targeting drugs to cancerous tissues and the tumor microenvironment. We briefly evaluate the structure and function of these receptor molecules, emphasizing the elegant mechanisms by which certain characteristics of cancer can be exploited in cancer treatment. After this discussion of receptors, we review their respective ligands and then the anticancer drugs delivered by nanotechnology in preclinical models of cancer. Ligand-functionalized nanocarriers have delivered significantly higher amounts of anticancer drugs in many in vitro and in vivo models of cancer compared to cancer models lacking such receptors or drug carrying nanocarriers devoid of ligand. This increased concentration of anticancer drug in the tumor site enabled by nanotechnology could have a major impact on the efficiency of cancer

  12. A conserved suppressor mutation in a tryptophan auxotroph results in dysregulation of Pseudomonas quinolone signal synthesis.

    Science.gov (United States)

    Knoten, Claire A; Wells, Greg; Coleman, James P; Pesci, Everett C

    2014-07-01

    Pseudomonas aeruginosa is a common nosocomial pathogen that relies on three cell-to-cell signals to regulate multiple virulence factors. The Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) is one of these signals, and it is known to be important for P. aeruginosa pathogenesis. PQS is synthesized in a multistep reaction that condenses anthranilate and a fatty acid. In P. aeruginosa, anthranilate is produced via the kynurenine pathway and two separate anthranilate synthases, TrpEG and PhnAB, the latter of which is important for PQS synthesis. Others have previously shown that a P. aeruginosa tryptophan auxotroph could grow on tryptophan-depleted medium with a frequency of 10(-5) to 10(-6). These revertants produced more pyocyanin and had increased levels of phnA transcript. In this study, we constructed similar tryptophan auxotroph revertants and found that the reversion resulted from a synonymous G-to-A nucleotide mutation within pqsC. This change resulted in increased pyocyanin and decreased PQS, along with an increase in the level of the pqsD, pqsE, and phnAB transcripts. Reporter fusion and reverse transcriptase PCR studies indicated that a novel transcript containing pqsD, pqsE, and phnAB occurs in these revertants, and quantitative real-time PCR experiments suggested that the same transcript appears in the wild-type strain under nutrient-limiting conditions. These results imply that the PQS biosynthetic operon can produce an internal transcript that increases anthranilate production and greatly elevates the expression of the PQS signal response protein PqsE. This suggests a novel mechanism to ensure the production of both anthranilate and PQS-controlled virulence factors. PMID:24748618

  13. Low-level quinolone-resistance in multi-drug resistant typhoid

    International Nuclear Information System (INIS)

    To find out the frequency of low-level quinolone-resistance in Multi-Drug Resistant (MDR) typhoid using nalidixic acid screening disc. Blood was obtained from suspected cases of typhoid fever and cultured in to BacT/ALERT. The positive blood cultures bottles were subcultured. The isolates were identified by colony morphology and biochemical tests using API-20E galleries. Susceptibility testing of isolates was done by modified Kirby-Bauer disc diffusion method on Muellar Hinton Agar. For the isolates, which were resistant to nalidixic acid by disc diffusion method, Minimal Inhibitory Concentrations (MICs) of ciprofloxacin and nalidixic acid were determined by using the E-test strips. Disc diffusion susceptibility tests and MICs were interpreted according to the guidelines provided by National Committee for Control Laboratory Standard (NCCLS). A total of 21(65.5%) out of 32 isolates of Salmonellae were nalidixic acid-resistant by disk diffusion method. All the nalidixic acid-resistant isolates by disc diffusion method were confirmed by MICs for both ciprofloxacin and nalidixic acid. All the nalidixic acid-resistant isolates had a ciprofloxacin MIC of 0.25-1 microg/ml (reduced susceptibility) and nalidixic acid MICs > 32 microg (resistant). Out of all Salmonella isolates, 24 (75%) were found to be MDR, and all were S. typbi. Low-level quinolone-resistance in typhoid was high in this small series. Screening for nalidixic acid resistance with a 30 microg nalidixic acid disk is a reliable and cost-effective method to detect low-level fluoroquinolone resistance, especially in the developing countries. (author)

  14. QUINOLONE- AND ETA-LACTAM- RESISTANCE IN Escherichia coli FROM DANISH AND ITALIAN BROILER FLOCKS

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-03-01

    Full Text Available The prevalence of quinolone- and -lactam-resistant E. coli was investigated among healthy broiler flocks in Denmark and Italy. In Denmark, sock samples were collected from 10 parent flocks and 10 offspring flocks, according to the procedure currently used for the surveillance of Salmonella in the EU. Samples were enriched in McConkey broth and streaked on McConkey agar plates added with nalidixic acid (32 g/ml, ciprofloxacin (2 g/ml, ampicillin (32 g/ml, cefotaxime (2 g/ml or ceftiofur (8 g/ml. The -glucuronidase test was performed for verification of presumptive E. coli. The same methods were used to analyse sock samples collected from 6 Italian broiler flocks. PCR with primers for the CTX-M-type extended-spectrum -lactamases (ESBLs was performed on cephalosporin-resistant isolates. While resistance to ampicillin and nalidixic acid was widespread in both countries, resistance to ciprofloxacin and cephalosporins was more common among Italian flocks. In Denmark, ciprofloxacin resistance was only detected in 1 parent flock without any history of quinolone usage and none of the flocks was positive for cephalosporin-resistant E. coli. In Italy, resistance to ciprofloxacin was detected in all flocks and resistance to ceftiofur and cefotaxime were detected in 5 flocks. Primers specific for the CTX-M-type ESBLs generated PCR amplicons from isolates from 3 of these flocks. In industrialized countries, the poultry production system is highly standardized, and therefore comparable. However, the use of broad-spectrum antimicrobials is particularly limited in Danish poultry production. Accordingly, the results of this study could reflect the different policies in antimicrobial usage between the two countries.

  15. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  16. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Ciprofloxacin-Nonsusceptible Escherichia coli and Klebsiella pneumoniae Isolated from Blood Cultures in Korea

    Directory of Open Access Journals (Sweden)

    Hee Young Yang

    2014-01-01

    Full Text Available OBJECTIVES:To analyze the prevalence of plasmid-mediated quinolone resistance (PMQR determinants in ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea.

  17. Plasmid-mediated quinolone resistance determinants in quinolone-resistant Escherichia coli isolated from patients with bacteremia in a university hospital in Taiwan, 2001-2015.

    Science.gov (United States)

    Kao, Cheng-Yen; Wu, Hsiu-Mei; Lin, Wei-Hung; Tseng, Chin-Chung; Yan, Jing-Jou; Wang, Ming-Cheng; Teng, Ching-Hao; Wu, Jiunn-Jong

    2016-01-01

    The aim of this study was to characterize fluoroquinolone (FQ)-resistant Escherichia coli isolates from bacteremia in Taiwan in 2001-2015. During the study period, 248 (21.2%) of 1171 isolates were identified as levofloxacin-resistant. The results of phylogenetic group analysis showed that 38.7% of the FQ-resistant isolates belonged to phylogenetic group B2, 23.4% to group B1, 22.6% to groupA, 14.9% to group D, and 0.4% belonged to group F. FQ-resistant isolates were highly susceptible to cefepime (91.5%), imipenem (96.0%), meropenem (98.8%), amikacin (98.0%), and fosfomycin (99.6%), as determined by the agar dilution method. β-lactamases, including blaTEM (66.1%), blaCMY-2 (16.5%), blaCTX-M (5.2%), blaDHA-1 (1.6%), and blaSHV-12 (1.6%), were found in FQ-resistant isolates. The results of PCR and direct sequencing showed that 37 isolates (14.9%) harbored plasmid-mediated quinolone resistance (PMQR) genes. qnrB2, qnrB4, qnrS1, coexistence of qnrB4 and qnrS1, oqxAB, and aac(6')-Ib-cr were found in 1, 4, 4, 1, 15, and 14 isolates, respectively. PMQR genes were successfully transfered for 11 (29.7%) of the 37 PMQR-harboring isolates by conjugation to E. coli C600. These findings indicate that qnr genes remained rare in E. coli but demonstrate the potential spread of oqxAB and aac(6')-Ib-c in Taiwan. PMID:27573927

  18. Characterization of antimicrobial resistance in Salmonella enterica food and animal isolates from Colombia: identification of a qnrB19-mediated quinolone resistance marker in two novel serovars

    DEFF Research Database (Denmark)

    Karczmarczyk, M.; Martins, M.; McCusker, M.;

    2010-01-01

    Ninety-three Salmonella isolates recovered from commercial foods and exotic animals in Colombia were studied. The serotypes, resistance profiles and where applicable the quinolone resistance genes were determined. Salmonella Anatum (n=14), Uganda (19), Braenderup (10) and Newport (10) were the most...... hitherto unrecognized in various Salmonella serovars in Colombia. We also report unusual high-level quinolone resistance in the absence of any DNA gyrase mutations in serovars S. Carrau, Muenchen and Uganda....

  19. Epidemiology of plasmid-mediated quinolone resistance determinants in bacterial isolates from animals and foods with co-resistance to several antibiotics

    OpenAIRE

    Ferreira, Eugénia; Francisco, Ana Patrícia; Jones-Dias, Daniela; Manageiro, Vera; Caniça, Manuela

    2011-01-01

    Background: The use of (fluoro)quinolones both in humans and animals has contributed to the selection of resistant bacteria, limiting the agents available for treatment. This study aims to search for plasmid-mediated quinolone resistance (PMQR) determinants to give information about these expanding resistance mechanisms, their capacity of dissemination among different bacteria by mobile elements, and the role that they play in facilitating co-resistance to several antimicrobials. Methods: ...

  20. Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity.

    Science.gov (United States)

    Han, Li-Chen; Stanley, Paul A; Wood, Paul J; Sharma, Pallavi; Kuruppu, Anchala I; Bradshaw, Tracey D; Moses, John E

    2016-08-21

    Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues. PMID:27443386

  1. Quinoxaline Nucleus: A Promising Scaffold in Anti-cancer Drug Discovery.

    Science.gov (United States)

    Pinheiro, Alessandra C; Mendonça Nogueira, Thais C; de Souza, Marcus V N

    2016-01-01

    Heterocyclic compounds are a class of substances, which play a critical role in modern drug discovery being incorporated in the structure of a large variety of drugs used in many different types of diseases. Quinoxaline is an important heterocyclic nucleus with a wide spectrum of biological activities, and recently much attention has been found on anticancer drug discovery based on this class. Owing to the importance of this system, the aim of this review is to provide an update on the synthesis and anticancer activity of quinoxaline derivatives covering articles published between 2010 and 2015.

  2. Molecular modeling based synthesis and evaluation of in vitro anticancer activity of indolyl chalcones.

    Science.gov (United States)

    Gaur, Rashmi; Yadav, Dharmendra K; Kumar, Shiv; Darokar, Mahendra P; Khan, Feroz; Bhakuni, Rajendra Singh

    2015-01-01

    A series of twenty one chalcone derivatives having indole moiety were synthesized and were evaluated against four human cancer cell lines. Indolyl chalcones 1a, 1b, 1d, 1f-1j, 2c, 2e, 2i showed good anticancer activity. Chalcones 1b and 1d were the most active and selective anticancer agents with IC50 values <1μg/ml and 1.51μg/ml, against WRL-68 cell line, respectively. Molecular mechanism was explored through in silico docking & ADMET studies. PMID:25860176

  3. 金属离子对喹诺酮活性影响的研究进展%Research Progress of Metal Ions Influence The Activity of Quinolone

    Institute of Scientific and Technical Information of China (English)

    范卓文; 朱丽华; 杨爽爽; 闫丽莉; 孙建华

    2014-01-01

    喹诺酮类药物以抗菌活性强、抗菌谱广、疗效确切等优点被广泛应用于临床,一些研究结果表明金属离子对喹诺酮类药物的活性有一定的影响。本文概述了喹诺酮类药物的发展及作用机制,总结了金属离子对喹诺酮类的作用及喹诺酮类药物金属配合物的活性,最后展望了喹诺酮类药物今后的发展。%Quinolone are widely used clinically because of its antibacterial activity, widely spectrum antimicrobial, curative ef-fect, etc.Some studies show that the metal ions affect the activity of quinolone.This paper outlines the development and action mecha-nism of quinolone. Summarizes the role of metal ions on metal quinolone and the biological activity of quinolone complexes. Finally, prospects of the development of quinolone.

  4. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  5. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency.

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin's self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  6. Quinoxaline-Based Scaffolds Targeting Tyrosine Kinases and Their Potential Anticancer Activity.

    Science.gov (United States)

    El Newahie, Aliya M S; Ismail, Nasser S M; Abou El Ella, Dalal A; Abouzid, Khaled A M

    2016-05-01

    Quinoxaline derivatives, also called benzopyrazines, are an important class of heterocyclic compounds. Quinoxalines have drawn great attention due to their wide spectrum of biological activities. They are considered as an important basis for anticancer drugs due to their potential activity as protein kinase inhibitors. In this review, we focus on the chemistry of the quinoxaline derivatives, the strategies for their synthesis, their potential activities against various tyrosine kinases, and on the structure-activity relationship studies reported to date.

  7. Pharmacokinetics of Sparfloxacin in the Serum and Vitreous Humor of Rabbits: Physicochemical Properties That Regulate Penetration of Quinolone Antimicrobials

    Science.gov (United States)

    Liu, Weiguo; Liu, Qing Feng; Perkins, Ruth; Drusano, George; Louie, Arnold; Madu, Assumpta; Mian, Umar; Mayers, Martin; Miller, Michael H.

    1998-01-01

    We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% ± 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (r2 > 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed Staphylococcus epidermidis decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin

  8. Luminescent determination of quinolones in milk samples by liquid chromatography/post-column derivatization with terbium oxide nanoparticles.

    Science.gov (United States)

    Yánez-Jácome, G S; Aguilar-Caballos, M P; Gómez-Hens, A

    2015-07-31

    The usefulness of terbium oxide nanoparticles (Tb4O7NPs) as post-column derivatizing reagent for the liquid chromatographic determination of residues of quinolone antibiotics in milk samples has been studied. Seven quinolones of veterinary use have been chosen as model analytes to develop this method. The derivatization step is based on the formation of luminescent chelates of quinolones with Tb4O7NPs, which are monitored at λex=340nm and λem=545nm. Another relevant feature of the method is that the use of a 10-cm column and a ternary mixture of methanol, acetonitrile and acetic acid as mobile phase in gradient elution mode allow the chromatographic separation of the quinolones in about 13min, whereas previously described chromatographic methods require about 20min. The dynamic ranges of the calibration graphs and limits of detection are, respectively: 65-900ngmL(-1) and 35ngmL(-1) for marbofloxacin, 7.2-900ngmL(-1) and 2.5ngmL(-1) for ciprofloxacin, 6-900ngmL(-1) and 2ngmL(-1) for danofloxacin, 50-900ngmL(-1) and 20ngmL(-1) for enrofloxacin, 35-900ngmL(-1) and 12ngmL(-1) for sarafloxacin, 5-900ngmL(-1) and 2ngmL(-1) for oxolinic acid, and 7-900ngmL(-1) and 2.5ngmL(-1) for flumequine. The precision, established at two concentration levels of each analyte and expressed as the percentage of the relative standard deviation is in the range of 1.9-8.1% using standards, and of 3.4-10.7% in the presence of milk samples. The method has been satisfactorily applied to the analysis of skimmed, semi-skimmed and whole milk samples, with recoveries ranging from 89.0 to 106.5%.

  9. A palladium-catalyzed intramolecular carbonylative annulation reaction for the synthesis of 4,5-fused tricyclic 2-quinolones.

    Science.gov (United States)

    Zhang, Xiwu; Liu, Haichao; Jia, Yanxing

    2016-06-01

    A concise and efficient synthetic route to 4,5-fused tricyclic 2-quinolones through the palladium-catalyzed carbonylative annulation of alkyne-tethered N-substituted o-iodoanilines has been developed. This reaction proceeds smoothly under mild reaction conditions and exhibits exceptional tolerance to a variety of functional groups. It has been successfully applied to the efficient synthesis of BI 224436, an HIV integrase inhibitor. PMID:27225232

  10. Comparative in vitro activities of newer quinolones against Pseudomonas species and Xanthomonas maltophilia isolated from patients with cancer.

    OpenAIRE

    Rolston, K V; Messer, M.; Ho, D H

    1990-01-01

    The in vitro susceptibilities of three Pseudomonas species (Pseudomonas aeruginosa, Pseudomonas putida, and Pseudomonas fluorescens) and Xanthomonas maltophilia to quinolone antimicrobial agents were determined. Several newer agents, particularly PD117558, PD117596, PD127391, sparfloxacin (AT-4140), A-56620, and temafloxacin, were active against Pseudomonas species. X. maltophilia isolates were generally less susceptible than were Pseudomonas isolates but were inhibited by some of the newer q...

  11. Prevalence and characterization of quinolone resistance mechanisms in commensal Escherichia coli isolated from slaughter animals in Poland, 2009-2012.

    Science.gov (United States)

    Wasyl, Dariusz

    2014-12-01

    The background of quinolone resistance was characterized in ciprofloxacin-resistant commensal Escherichia coli selected out of 3,551 isolates from slaughtered animals in Poland between 2009 and 2012. Plasmid-mediated determinants were suspected in 6.2% of the study group, ranging from 1.1% in cattle to 9.7% in turkeys. Polymerase chain reaction and sequencing identified up to four quinolone resistance-determining substitutions in gyrA (Ser83, Asp87) and parC (Ala56, Ser80). Plasmid-mediated mechanisms were identified as qnrS1 (or qnrS3, n=70, including six isolates with chromosomal mutations), qnrB19 (or qnrB10, n=19), and qnrB17 (n=1). All tested isolates were negative for qnrA, qnrC, qnrD, qepA, and aac(6')-Ib-cr. Still, there were several E. coli suspected for both plasmid- and chromosome-mediated resistance with unrevealed genetic background of the phenomenon. Since all tested isolates showed diverse XbaI-PFGE profiles, chromosome-encoded quinolone resistance does not result from the spread of a single resistant clone, however, it is rather due to antimicrobial pressure leading to the selection of random gyr and par mutants. It also favors the selection and spread of plasmids carrying predominant qnr genes, since the same determinants were found in Salmonella, isolated from similar sources. The identification of carrier plasmids and mitigation of their spread might be essential for sustainable quinolone usage in animal husbandry and efficient protection of human health. PMID:25051094

  12. Anticancer activity of Cyanothece sp. strain extracts from Egypt:First record

    Institute of Scientific and Technical Information of China (English)

    Nermin Adel El Semary; Manar Fouda

    2015-01-01

    Objective: To assess the anticancer activity of eight cyanobacterial hydrophilic extracts on Ehrlich ascites carcinoma cell line. Methods: The cyanobacterial strains used in the investigation were collected from diverse habitats in Egypt. The initial cytotoxicity test of cyanobacterial hydrophilic ex-tracts was carried out by MTT assay. The in vitro anticancer activity of the four most active extracts was performed on MCF-7 cells using sulforhodamine B assay. Morpho-logical and molecular techniques were used to characterise identity of the isolate from which the most potent cytotoxic extract was obtained. Results: Extracts from four cyanobacterial strains had higher cytotoxic activities scoring 76.68%, 77.70%, 76.70%and 74.45%, respectively. A considerable anticancer effect was only detected when the concentrated extracts were used. One cyanobacterial extract gave the highest anticancer activity on human breast adenocarcinoma cell line (57.6% of in-hibition) as compared to control. The isolate was best-matched to Cyanothece sp. with sequence resemblance 98% to Cyanothece sp. strain PCC7564 and the phylogenetic analysis confirmed its close identity to the Cyanothece genus. Conclusions: This is the first study to report the anticancer effect of aqueous extracts derived from the unicellular Cyanothece sp. from Egypt and its potential as a plausible candidate for future mass biotechnological applications.

  13. Interactions of the "piano-stool" [ruthenium(II)(η(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study.

    Science.gov (United States)

    Zábojníková, Tereza; Cajzl, Radim; Kljun, Jakob; Chval, Zdeněk; Turel, Iztok; Burda, Jaroslav V

    2016-07-15

    Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ∼6 kcal/mol) in basic environment. © 2016 Wiley Periodicals, Inc. PMID:27185047

  14. Interactions of the "piano-stool" [ruthenium(II)(η(6) -arene)(quinolone)Cl](+) complexes with water; DFT computational study.

    Science.gov (United States)

    Zábojníková, Tereza; Cajzl, Radim; Kljun, Jakob; Chval, Zdeněk; Turel, Iztok; Burda, Jaroslav V

    2016-07-15

    Full optimizations of stationary points along the reaction coordinate for the hydration of several quinolone Ru(II) half-sandwich complexes were performed in water environment using the B3PW91/6-31+G(d)/PCM/UAKS method. The role of diffuse functions (especially on oxygen) was found crucial for correct geometries along the reaction coordinate. Single-point (SP) calculations were performed at the B3LYP/6-311++G(2df,2pd)/DPCM/saled-UAKS level. In the first part, two possible reaction mechanisms-associative and dissociative were compared. It was found that the dissociative mechanism of the hydration process is kinetically slightly preferred. Another important conclusion concerns the reaction channels. It was found that substitution of chloride ligand (abbreviated in the text as dechlorination reaction) represents energetically and kinetically the most feasible pathway. In the second part the same hydration reaction was explored for reactivity comparison of the Ru(II)-complexes with several derivatives of nalidixic acid: cinoxacin, ofloxacin, and (thio)nalidixic acid. The hydration process is about four orders of magnitude faster in a basic solution compared to neutral/acidic environment with cinoxacin and nalidixic acid as the most reactive complexes in the former and latter environments, respectively. The explored hydration reaction is in all cases endergonic; nevertheless the endergonicity is substantially lower (by ∼6 kcal/mol) in basic environment. © 2016 Wiley Periodicals, Inc.

  15. Source attribution of human Campylobacter isolates by MLST and fla-typing and association of genotypes with quinolone resistance.

    Science.gov (United States)

    Kittl, Sonja; Heckel, Gerald; Korczak, Bożena M; Kuhnert, Peter

    2013-01-01

    Campylobacteriosis is the most frequent zoonosis in developed countries and various domestic animals can function as reservoir for the main pathogens Campylobacter jejuni and Campylobacter coli. In the present study we compared population structures of 730 C. jejuni and C. coli from human cases, 610 chicken, 159 dog, 360 pig and 23 cattle isolates collected between 2001 and 2012 in Switzerland. All isolates had been typed with multi locus sequence typing (MLST) and flaB-typing and their genotypic resistance to quinolones was determined. We used complementary approaches by testing for differences between isolates from different hosts with the proportion similarity as well as the fixation index and by attributing the source of the human isolates with Bayesian assignment using the software STRUCTURE. Analyses were done with MLST and flaB data in parallel and both typing methods were tested for associations of genotypes with quinolone resistance. Results obtained with MLST and flaB data corresponded remarkably well, both indicating chickens as the main source for human infection for both Campylobacter species. Based on MLST, 70.9% of the human cases were attributed to chickens, 19.3% to cattle, 8.6% to dogs and 1.2% to pigs. Furthermore we found a host independent association between sequence type (ST) and quinolone resistance. The most notable were ST-45, all isolates of which were susceptible, while for ST-464 all were resistant. PMID:24244747

  16. Source attribution of human Campylobacter isolates by MLST and fla-typing and association of genotypes with quinolone resistance.

    Directory of Open Access Journals (Sweden)

    Sonja Kittl

    Full Text Available Campylobacteriosis is the most frequent zoonosis in developed countries and various domestic animals can function as reservoir for the main pathogens Campylobacter jejuni and Campylobacter coli. In the present study we compared population structures of 730 C. jejuni and C. coli from human cases, 610 chicken, 159 dog, 360 pig and 23 cattle isolates collected between 2001 and 2012 in Switzerland. All isolates had been typed with multi locus sequence typing (MLST and flaB-typing and their genotypic resistance to quinolones was determined. We used complementary approaches by testing for differences between isolates from different hosts with the proportion similarity as well as the fixation index and by attributing the source of the human isolates with Bayesian assignment using the software STRUCTURE. Analyses were done with MLST and flaB data in parallel and both typing methods were tested for associations of genotypes with quinolone resistance. Results obtained with MLST and flaB data corresponded remarkably well, both indicating chickens as the main source for human infection for both Campylobacter species. Based on MLST, 70.9% of the human cases were attributed to chickens, 19.3% to cattle, 8.6% to dogs and 1.2% to pigs. Furthermore we found a host independent association between sequence type (ST and quinolone resistance. The most notable were ST-45, all isolates of which were susceptible, while for ST-464 all were resistant.

  17. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry).

    Science.gov (United States)

    Zhao, Tiejun; Sun, Qiang; Marques, Maud; Witcher, Michael

    2015-01-01

    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  18. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    2015-01-01

    Full Text Available There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  19. Anticancer activity of Carica papaya: a review.

    Science.gov (United States)

    Nguyen, Thao T T; Shaw, Paul N; Parat, Marie-Odile; Hewavitharana, Amitha K

    2013-01-01

    Carica papaya is widely cultivated in tropical and subtropical countries and is used as food as well as traditional medicine to treat a range of diseases. Increasing anecdotal reports of its effects in cancer treatment and prevention, with many successful cases, have warranted that these pharmacological properties be scientifically validated. A bibliographic search was conducted using the key words "papaya", "anticancer", and "antitumor" along with cross-referencing. No clinical or animal cancer studies were identified and only seven in vitro cell-culture-based studies were reported; these indicate that C. papaya extracts may alter the growth of several types of cancer cell lines. However, many studies focused on specific compounds in papaya and reported bioactivity including anticancer effects. This review summarizes the results of extract-based or specific compound-based investigations and emphasizes the aspects that warrant future research to explore the bioactives in C. papaya for their anticancer activities.

  20. Some medicinal plants as natural anticancer agents

    Directory of Open Access Journals (Sweden)

    Govind Pandey

    2009-01-01

    Full Text Available India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance against infection by re-stabilizing body equilibrium and conditioning the body tissues. Several reports describe that the anticancer activity of medicinal plants is due to the presence of antioxidants in them. In fact, the medicinal plants are easily available, cheaper and possess no toxicity as compared to the modern (allopathic drugs. Hence, this review article contains 66 medicinal plants, which are the natural sources of anticancer agents.

  1. Studies with Myrtus communis L.: Anticancer properties.

    Science.gov (United States)

    Ogur, Recai

    2014-01-01

    Myrtus communis (MC) L. is a well-known Mediterranean plant with important cultural significance in this region. In ancient times, MC was accepted as a symbol of immortality. Maybe due to this belief, it is used during cemetery visits in some regions. Although it is a well-known plant in cosmetics, and there is a lot of studies about its different medical properties, anticancer studies performed using its different extracts or oils are not so much, but increasing. We collected these anticancer property-related studies in this review. PMID:26401362

  2. Magnetic polymer nanospheres for anticancer drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J [Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice (Slovakia); Muckova, M, E-mail: akasard@saske.s [Hameln rds a.s., 900 01 Modra (Slovakia)

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  3. Quinolone co-resistance in ESBL- or AmpC-producing Escherichia coli from an Indian urban aquatic environment and their public health implications.

    Science.gov (United States)

    Bajaj, Priyanka; Kanaujia, Pawan Kumar; Singh, Nambram Somendro; Sharma, Shalu; Kumar, Shakti; Virdi, Jugsharan Singh

    2016-01-01

    Quinolone and β-lactam antibiotics constitute major mainstay of treatment against infections caused by pathogenic Escherichia coli. Presence of E. coli strains expressing co-resistance to both these antibiotic classes in urban aquatic environments which are consistently being used for various anthropogenic activities represents a serious public health concern. From a heterogeneous collection of 61 E. coli strains isolated from the river Yamuna traversing through the National Capital Territory of Delhi (India), those harboring blaCTX-M-15 (n = 10) or blaCMY-42 (n = 2) were investigated for co-resistance to quinolones and the molecular mechanisms thereof. Resistance was primarily attributed to amino acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA (S83L ± D87N) and ParC (S80I ± E84K). One of the E. coli strains, viz., IPE, also carried substitutions in GyrB and ParE at positions Ser492→Asn and Ser458→Ala, respectively. The phenotypically susceptible strains nevertheless carried plasmid-mediated quinolone resistance (PMQR) gene, viz., qnrS, which showed co-transfer to the recipient quinolone-sensitive E. coli J53 along with the genes encoding β-lactamases and led to increase in minimal inhibitory concentrations of quinolone antibiotics. To the best of our knowledge, this represents first report of molecular characterization of quinolone co-resistance in E. coli harboring genes for ESBLs or AmpC β-lactamases from a natural aquatic environment of India. The study warrants true appreciation of the potential of urban aquatic environments in the emergence and spread of multi-drug resistance and underscores the need to characterize resistance genetic elements vis-à-vis their public health implications, irrespective of apparent phenotypic resistance.

  4. A Journey Under the Sea: The Quest for Marine Anti-Cancer Alkaloids

    Directory of Open Access Journals (Sweden)

    Nadine Darwiche

    2011-11-01

    Full Text Available The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many are now being tested in various phases of clinical trials. Recently, marine-derived alkaloids, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to also exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and tubulin polymerization, and induction of apoptosis and cytotoxicity. Two tunicate-derived alkaloids, aplidin and trabectedin, offer promising drug profiles, and are currently in phase II clinical trials against several solid and hematologic tumors. This review sheds light on the rich array of anti-cancer alkaloids in the marine ecosystem and introduces the most investigated compounds and their mechanisms of action.

  5. A journey under the sea: the quest for marine anti-cancer alkaloids.

    Science.gov (United States)

    Tohme, Rita; Darwiche, Nadine; Gali-Muhtasib, Hala

    2011-01-01

    The alarming increase in the global cancer death toll has fueled the quest for new effective anti-tumor drugs thorough biological screening of both terrestrial and marine organisms. Several plant-derived alkaloids are leading drugs in the treatment of different types of cancer and many are now being tested in various phases of clinical trials. Recently, marine-derived alkaloids, isolated from aquatic fungi, cyanobacteria, sponges, algae, and tunicates, have been found to also exhibit various anti-cancer activities including anti-angiogenic, anti-proliferative, inhibition of topoisomerase activities and tubulin polymerization, and induction of apoptosis and cytotoxicity. Two tunicate-derived alkaloids, aplidin and trabectedin, offer promising drug profiles, and are currently in phase II clinical trials against several solid and hematologic tumors. This review sheds light on the rich array of anti-cancer alkaloids in the marine ecosystem and introduces the most investigated compounds and their mechanisms of action. PMID:22113577

  6. Synthesis, Anticancer and Antibacterial Activity of Salinomycin N-Benzyl Amides

    Directory of Open Access Journals (Sweden)

    Michał Antoszczak

    2014-11-01

    Full Text Available A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA and Staphylococcus epidermidis (MRSE, and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.

  7. Identification of an integron containing the quinolone resistance gene qnrA1 in Shewanella xiamenensis.

    Science.gov (United States)

    Zhao, Jing-yi; Mu, Xiao-dong; Zhu, Yuan-qi; Xi, Lijun; Xiao, Zijun

    2015-09-01

    This study investigated multidrug resistance in Shewanella xiamenensis isolated from an estuarine water sample in China during 2014. This strain displayed resistance or decreased susceptibility to ampicillin, aztreonam, cefepime, cefotaxime, chloramphenicol, ciprofloxacin, erythromycin, kanamycin and trimethoprim-sulfamethoxazole. The antimicrobial resistance genes aacA3, blaOXA-199, qnrA1 and sul1 were identified by PCR amplification and by sequencing. Pulsed-field gel electrophoresis and DNA hybridization experiments showed that the quinolone resistance gene qnrA1 was chromosomally located. qnrA1 was located in a complex class 1 integron, downstream from an ISCR1, and bracketed by two copies of qacEΔ1-sul1 genes. This integron is similar to In825 with four gene cassettes aacA3, catB11c, dfrA1z and aadA2az. An IS26-mel-mph2-IS26 structure was also detected in the flanking sequences, conferring resistance to macrolides. This is the first identification of the class 1 integron in S. xiamenensis. This is also the first identification of the qnrA1 gene and IS26-mediated macrolide resistance genes in S. xiamenensis. Presence of a variety of resistance genetic determinants in environmental S. xiamenensis suggests the possibility that this species may serve as a potential vehicle of antimicrobial resistance genes in aquatic environments. PMID:26316545

  8. Application of Sigmoidal Transformation Functions in Optimization of Micellar Liquid Chromatographic Separation of Six Quinolone Antibiotics.

    Science.gov (United States)

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2016-03-01

    A chemometrics approach has been used to optimize the separation of six quinolone compounds by micellar liquid chromatography (MLC). A Derringer's desirability function, a multicriteria decision-making (MCDM) method, was tested for evaluation of two different measures of chromatographic performance (resolution and analysis time). The effect of three experimental parameters on a chromatographic response function (CRF) expressed as a product of two sigmoidal desirability functions was investigated. The sigmoidal functions were used to transform the optimization criteria, resolution and analysis time into the desirability values. The factors studied were the concentration of sodium dodecyl sulfate, butanol content and pH of the mobile phase. The experiments were done according to the face-centered cube central composite design, and the calculated CRF values were fitted to a polynomial model to correlate the CRF values with the variables and their interactions. The developed regression model showed good descriptive and predictive ability (R(2) = 0.815, F = 6.919, SE = 0.038, [Formula: see text]) and used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture. The efficiency of prediction of polynomial model was confirmed by performing the experiment under the optimal conditions.

  9. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596.

    Science.gov (United States)

    Gough, A; Johnson, R; Campbell, E; Hall, L; Tylor, J; Carpenter, A; Black, W; Basrur, P K; Baragi, V M; Sigler, R; Metz, A

    1996-06-01

    To study the potential of the fluorquinolone, PD 117596 to cause arthropathy in experimental animals, immature rabbits were orally administered the drug for five days at 0, 100, 350, 500 and 750 mg/kg. Characterization of changes induced in major synovial joints was based on: macroscopic and histopathologic observations, transmission electron microscopic examinations and magnetic resonance imaging. Preferentially targeting the knee, PD 117596 produced vesicles and erosions in articular cartilage which resembled, morphologically, those described in other laboratory species. Lesion incidence was not clearly dose-related. In the perivesicular region, degenerate chondrocytes were intermixed with hypertrophic cartilage cells and chondrocyte clusters. Ultrastructurally, hypertrophic chondrocytes were the consequence of karyomegaly and RER proliferation. Matrix density was reduced due to collagen and proteoglycan loss. Joint structures were readily visualized by magnetic resonance imaging which identified thickened articular cartilage, surface irregularities consistent with ruptured vesicles and separation of opposing articular surfaces secondary to synovival effusions. The immature rabbit, although less sensitive than the juvenile dog to the arthropathic effects of quinolones, was nonetheless a good model to study this experimental osteoarticular disease.

  10. Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-08-01

    Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(ΙΙΙ), Zr(ΙV) and U(VΙ) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

  11. Application of Sigmoidal Transformation Functions in Optimization of Micellar Liquid Chromatographic Separation of Six Quinolone Antibiotics.

    Science.gov (United States)

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2016-03-01

    A chemometrics approach has been used to optimize the separation of six quinolone compounds by micellar liquid chromatography (MLC). A Derringer's desirability function, a multicriteria decision-making (MCDM) method, was tested for evaluation of two different measures of chromatographic performance (resolution and analysis time). The effect of three experimental parameters on a chromatographic response function (CRF) expressed as a product of two sigmoidal desirability functions was investigated. The sigmoidal functions were used to transform the optimization criteria, resolution and analysis time into the desirability values. The factors studied were the concentration of sodium dodecyl sulfate, butanol content and pH of the mobile phase. The experiments were done according to the face-centered cube central composite design, and the calculated CRF values were fitted to a polynomial model to correlate the CRF values with the variables and their interactions. The developed regression model showed good descriptive and predictive ability (R(2) = 0.815, F = 6.919, SE = 0.038, [Formula: see text]) and used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture. The efficiency of prediction of polynomial model was confirmed by performing the experiment under the optimal conditions. PMID:26590234

  12. "Ziziphus jujuba": A red fruit with promising anticancer activities

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2015-01-01

    Full Text Available Ziziphus jujuba Mill. (Z. jujuba is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers,  including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.

  13. Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

    Directory of Open Access Journals (Sweden)

    Demet Coşkun

    2016-01-01

    Full Text Available Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl-2-propanones propenones (3a–f, were designed, synthesized, and characterized. In vitro antitumor activities of the newly synthesized (3a–f and previously synthesized (3g–j chalcone compounds were determined by using human breast (MCF-7 and prostate (PC-3 cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cell viability assay for the tested chalcone compounds was performed and the log⁡IC50 values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines (p<0.05.

  14. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the "Supply Problem".

    Science.gov (United States)

    Gomes, Nelson G M; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

    2016-05-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors' opinion should be pursued due to their most promising anticancer activities. PMID:27213412

  15. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    Science.gov (United States)

    Gomes, Nelson G. M.; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

    2016-01-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. PMID:27213412

  16. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    Directory of Open Access Journals (Sweden)

    Nelson G. M. Gomes

    2016-05-01

    Full Text Available Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities.

  17. Seawater is a reservoir of multi-resistant Escherichia coli, including strains hosting plasmid-mediated quinolones resistance and extended-spectrum beta-lactamases genes

    Directory of Open Access Journals (Sweden)

    Marta S. Alves

    2014-08-01

    Full Text Available The aim of this study was to examine antibiotic resistance (AR dissemination in coastal water, considering the contribution of different sources of faecal contamination. Samples were collected in Berlenga, an uninhabited island classified as Natural Reserve and visited by tourists for aquatic recreational activities. To achieve our aim, AR in Escherichia coli isolates from coastal water was compared to AR in isolates from two sources of faecal contamination: human-derived sewage and seagull faeces. Isolation of E. coli was done on Chromocult agar. Based on genetic typing 414 strains were established. Distribution of E. coli phylogenetic groups was similar among isolates of all sources. Resistances to streptomycin, tetracycline, cephalothin and amoxicillin were the most frequent. Higher rates of AR were found among seawater and faeces isolates, except for last-line antibiotics used in human medicine. Multi-resistance rates in isolates from sewage and seagull faeces (29% and 32% were lower than in isolates from seawater (39%. Seawater AR profiles were similar to those from seagull faeces and differed significantly from sewage AR profiles. Nucleotide sequences matching resistance genes blaTEM, sul1, sul2, tet(A and tet(B, were present in isolates of all sources. Genes conferring resistance to 3rd generation cephalosporins were detected in seawater (blaCTX-M-1 and blaSHV-12 and seagull faeces (blaCMY-2. Plasmid-mediated determinants of resistance to quinolones were found: qnrS1 in all sources and qnrB19 in seawater and seagull faeces. Our results show that seawater is a relevant reservoir of AR and that seagulls are an efficient vehicle to spread human-associated bacteria and resistance genes. The E. coli resistome recaptured from Berlenga coastal water was mainly modulated by seagulls-derived faecal pollution. The repertoire of resistance genes covers antibiotics critically important for humans, a potential risk for human health.

  18. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast

    Science.gov (United States)

    Li, Yanran; Smolke, Christina D.

    2016-01-01

    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4′-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery. PMID:27378283

  19. Anticancer activity of botanical compounds in ancient fermented beverages (review).

    Science.gov (United States)

    McGovern, P E; Christofidou-Solomidou, M; Wang, W; Dukes, F; Davidson, T; El-Deiry, W S

    2010-07-01

    Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.

  20. Anticancer activity of botanical compounds in ancient fermented beverages (review).

    Science.gov (United States)

    McGovern, P E; Christofidou-Solomidou, M; Wang, W; Dukes, F; Davidson, T; El-Deiry, W S

    2010-07-01

    Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future. PMID:20514391

  1. Why Anticancer Nanomedicine Needs Sugars?

    Science.gov (United States)

    Bouffard, E; El Cheikh, K; Gallud, A; Da Silva, A; Maynadier, M; Basile, I; Gary-Bobo, M; Morere, A; Garcia, M

    2015-01-01

    Nowadays, nanomedicine brings new opportunities for diagnosis and treatment through innovative combinations of materials structured at the nanoscale, biomolecules and physicochemical processes. If the intrinsic properties of nanomaterials appear of major importance in this new discipline, the functionalization of these nanotools with biomolecules improves both their biocompatibility and efficacy. This is the case of carbohydrate derivatives, natural or synthetic, which are increasingly being used in nanostructures for medical purposes. As in current medicine, sugars are used to mimic their physiological roles. Indeed, carbohydrates enhance the solubility and reduce the clearance of drugs. They are used to mask immunogenic components of nano-objects and escape the body defenses and finally facilitate the delivery to the target tissue. All these properties explain the growing importance of sugars in nanomedicine.

  2. Intravenous nursing progress quinolones The research progress of nursing on quinolones with intravenous injection%喹诺酮类药物静脉应用护理进展

    Institute of Scientific and Technical Information of China (English)

    杨希芳; 王静; 胡玉美

    2011-01-01

    对喹诺酮类药物的用药现状、不良反应及护理、配伍禁忌等进行了综述,旨在提高护理员对该药的认识,以提高疗效,保证用药安全。%Status of quinolones, adverse reactions and nursing, incompatibility etc.were reviewed, In order to improve cognition of care workers for the drugs, to improve efficacy and ensure safety of drugs.

  3. Susceptibility to β-lactams and quinolones of Enterobacteriaceae isolated from urinary tract infections in outpatients

    Directory of Open Access Journals (Sweden)

    Martín Marchisio

    2015-01-01

    Full Text Available AbstractThe antibiotic susceptibility profile was evaluated in 71 Enterobacteriaceae isolates obtained from outpatient urine cultures in July 2010 from two health institutions in Santa Fe, Argentina. The highest rates of antibiotic resistance were observed for ampicillin (AMP (69%, trimethoprim/sulfamethoxazole (TMS (33%, and ciprofloxacin (CIP (25%. Meanwhile, 21% of the isolates were resistant to three or more tested antibiotics families. Thirty integron-containing bacteria (42.3% were detected, and a strong association with TMS resistance was found. Third generation cephalosporin resistance was detected in only one Escherichia coli isolate, and it was characterized as a blaCMY-2 carrier. No plasmid-mediated quinolone resistance (PMQR was found. Resistance to fluoroquinolone in the isolates was due to alterations in QRDR regions. Two mutations in GyrA (S83L, D87N and one in ParC (S80I were observed in all CIP-resistant E. coli. It was determined to be the main phylogenetic groups in E. coli isolates. Minimum Inhibitory Concentration (MIC values against nalidixic acid (NAL, levofloxacin (LEV, and CIP were determined for 63 uropathogenic E. coli isolates as MIC50 of 4 μg/mL, 0.03125 μg/mL, and 0.03125 μg/mL, respectively, while the MIC90 values of the antibiotics were determined as 1024 μg/mL, 64 μg/mL, and 16 μg/mL, respectively. An association between the phylogenetic groups, A and B1 with fluoroquinolone resistance was observed. These results point to the importance of awareness of the potential risk associated with empirical treatment with both the families of antibiotics.

  4. In vitro susceptibility pattern of acinetobacter species to commonly used cephalosporins, quinolones, and aminoglycosides

    Directory of Open Access Journals (Sweden)

    Prashanth K

    2004-01-01

    Full Text Available PURPOSE: Acinetobacter spp. is an emerging important nosocomial pathogen. Clinical isolates of this genus are often resistant to many antibiotics. The in vitro susceptibility of Acinetobacter isolates obtained from patients were tested for currently used antibiotics. In addition, the study aimed at biotyping of Acinetobacter baumannii. METHODS: A total of 66 isolates were phenotypically characterised through a large panel of 25 carbon assimilation tests and susceptibility through disc diffusion method with 10 antimicrobial agents were tested. MICs were determined only for second line broad-spectrum drugs such as cefotaxime, ceftazidime, amikacin, ciprofloxacin, and ofloxacin using NCCLS guidelines. RESULTS: Multiple drug resistance (MDR was only witnessed in A. baumannii and not in other Acinetobacter species. Aminoglycosides such as amikacin, netilmicin were most active against the MDR isolates tested (60% susceptibility. Ceftazidime was more active than cefotaxime. MDR A. baumannii strains were susceptible only to amikacin, netilmicin and ceftadizime. Ciprofloxacin had poor activity irrespective of isolates belonging to different DNA groups tested (58% resistance overall, 79% among A. baumannii. Strains of Biotypes 6 and 19 of A. baumannii showed broader resistance than those of biotype 10 and others. CONCLUSIONS: Strains of A. baumannii from patients in our hospital, were generally more resistant to quinolones, -lactam antibiotics, first and second generation cephalosporins and partially resistant to third generation cephalosporins and aminoglycosides. The strains belonging to other DNA groups of Acinetobacter were comparatively less resistant than A.baumannii, except ciprofloxacin. This study suggests that, a combination therapy, using a third generation cephalosporin and amikacin, would be best choice for treating Acinetobacter infections.

  5. Changes of the Quinolones Resistance to Gram-positive Cocci Isolated during the Past 8 Years in the First Bethune Hospital

    Science.gov (United States)

    Xu, Jiancheng; Chen, Qihui; Yao, Hanxin; Zhou, Qi

    This study was to investigate the quinolones resistance to gram-positive cocci isolated in the First Bethune Hospital during the past 8 years. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). The rates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCNS) were 50.8%∼83.3% and 79.4%∼81.5%during the past 8 years, respectively. In recent 8 years, the quinolones resistance to gram-positive cocci had increased. Monitoring of the quinolones resistance to gram-positive cocci should be strengthened. The change of the antimicrobial resistance should be investigated in order to guide rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  6. Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.

    Science.gov (United States)

    Arakawa, Hiroshi; Kamioka, Hiroki; Kanagawa, Masahiko; Hatano, Yasuko; Idota, Yoko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction. PMID:26590007

  7. ANALYSES OF QUINOLONE ANTIMICROBIALS IN HUMAN PLASMA BY CAPILLARY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY/FAST ATOM BOMBARDMENT MASS SPECTROMETRY

    OpenAIRE

    Hattori, Hideki; Suzuki, Osamu; Seno, Hiroshi; Ishii, Akira; Yamada, Takamichi

    1993-01-01

    Capillary high-performance liquid chromatography (HPLC) was combined with frit fast atom bombardment (FAB)-mass spectrometry (MS) , and a detailed procedure has been established for on-line analysis of ten quinolone antimicrobials in human plasma by the HPLC/FAB-MS. A special column switching device for concentration enabled injection of as large as a 500 μl sample; and the capillary column (0.5 mm i. d.) enabled introduction of its entire effluent to the frit interface of FAB-MS. These condi...

  8. Enantioselective Intermolecular [2 + 2] Photocycloaddition Reactions of 2(1H)-Quinolones Induced by Visible Light Irradiation.

    Science.gov (United States)

    Tröster, Andreas; Alonso, Rafael; Bauer, Andreas; Bach, Thorsten

    2016-06-29

    In the presence of a chiral thioxanthone catalyst (10 mol %) the title compounds underwent a clean intermolecular [2 + 2] photocycloaddition with electron-deficient olefins at λ = 419 nm. The reactions not only proceeded with excellent regio- and diastereoselectivity but also delivered the respective cyclobutane products with significant enantiomeric excess (up to 95% ee). Key to the success of the reactions is a two-point hydrogen bonding between quinolone and catalyst enabling efficient energy transfer and high enantioface differentiation. Preliminary work indicated that solar irradiation can be used for this process and that the substrate scope can be further expanded to isoquinolones. PMID:27268908

  9. 喹诺酮类药物临床应用及不良反应%Clinical application of quinolone antibiotics and analysis of adverse reactions

    Institute of Scientific and Technical Information of China (English)

    戴丽

    2012-01-01

    OBJECTIVE To analyze the structure feature of quinolone antibacterials, antibacterial spectrum and clinical application and adverse reactions. METHODS The clinical prescriptions on quinolone antibacterial statistics in 2010 were analyzed, including the drug using times, frequency and sorting, as well as the using purpose of quinolone drugs and the effects. RESULTS The quinolone drug using frequency = appearing times of a drug on prescriptions/total number of prescriptions. The top three antibiotics most frequently used were nofloxacin, ciprofloxacin and ofloxacin, which were widely used and accounted for 85. 3% of quinolone prescription drugs on prescriptions. CONCLUSION Quinolone drugs are important antibiotics which should be used reasonably and standardly to avoid adverse drug reactions.%目的 对喹诺酮类抗菌药物的结构特点、抗菌谱及临床应用范围、不良反应进行分析.方法 对医院2010年喹诺酮类抗菌药物临床处方进行统计,分析其药品临床使用处方数、频率和排序及喹诺酮类药物的用途及作用.结果 喹诺酮类药物使用频率=药品处方数/药品总处方数,其中使用频率最高的前3位为诺氟沙星、依诺沙星和氧氟沙星,占喹诺酮类抗菌药物处方总量的85.3%,在抗菌药物中运用广泛.结论 喹诺酮类在抗菌药物中占有重要地位,应规范、合理应用,防止造成药物不良反应.

  10. Toxicities of anticancer drugs and its management

    Directory of Open Access Journals (Sweden)

    Ambili Remesh

    2012-02-01

    Full Text Available One of the characteristics that distinguish anticancer agents from other drugs is the frequency and severity of side effects at therapeutic doses. Most cytotoxic drugs target rapidly multiplying cells and the putative targets are the nucleic acids and their precursors, which are rapidly synthesised during cell division. Many solid tumours have a lower growth fraction than the normal bone marrow, gastro intestinal lining, reticuloendothelial system and gonads. Drugs affect these tissues in a dose dependant manner and there is individual susceptibility also. So toxicities are more frequently associated with these tissues. The side effects may be acute or chronic, self-limited, permanent, mild or potentially life threatening. Management of these side effects is of utmost importance because they affect the treatment, tolerability and overall quality of life. This paper gives an overview of different toxicities of anticancer drugs and its management. [Int J Basic Clin Pharmacol 2012; 1(1.000: 2-12

  11. Transcription factors as targets of anticancer drugs.

    Science.gov (United States)

    Gniazdowski, M; Czyz, M

    1999-01-01

    Several general and gene- and cell-selective transcription factors are required for specific transcription to occur. Many of them exert their functions through specific contacts either in the promoter region or at distant sequences regulating the initiation. These contacts may be altered by anticancer drugs which form non-covalent complexes with DNA. Covalent modifications of DNA by alkylating agents may prevent transcription factors from recognizing their specific sequences or may constitute multiple "unnatural" binding sites in DNA which attract the factors thus decreasing their availability in the cell. The anticancer drug-transcription factor interplay which is based on specific interactions with DNA may contribute to pharmacological properties of the former and provide a basis for the search for new drugs. PMID:10547027

  12. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance.

    Science.gov (United States)

    Pietrocola, Federico; Pol, Jonathan; Vacchelli, Erika; Rao, Shuan; Enot, David P; Baracco, Elisa E; Levesque, Sarah; Castoldi, Francesca; Jacquelot, Nicolas; Yamazaki, Takahiro; Senovilla, Laura; Marino, Guillermo; Aranda, Fernando; Durand, Sylvère; Sica, Valentina; Chery, Alexis; Lachkar, Sylvie; Sigl, Verena; Bloy, Norma; Buque, Aitziber; Falzoni, Simonetta; Ryffel, Bernhard; Apetoh, Lionel; Di Virgilio, Francesco; Madeo, Frank; Maiuri, Maria Chiara; Zitvogel, Laurence; Levine, Beth; Penninger, Josef M; Kroemer, Guido

    2016-07-11

    Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. PMID:27411589

  13. Reengineered tricyclic anti-cancer agents.

    Science.gov (United States)

    Kastrinsky, David B; Sangodkar, Jaya; Zaware, Nilesh; Izadmehr, Sudeh; Dhawan, Neil S; Narla, Goutham; Ohlmeyer, Michael

    2015-10-01

    The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID:26372073

  14. Human Tumor Xenograft Models for Preclinical Assessment of Anticancer Drug Development

    OpenAIRE

    Jung, Joohee

    2014-01-01

    Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-der...

  15. [Quod medicina aliis, aliis est acre venenum**--venoms as a source of anticancer agents].

    Science.gov (United States)

    Kucińska, Małgorzata; Ruciński, Piotr; Murias, Marek

    2013-01-01

    Natural product derived from plants and animals were used in folk medicine for centuries. The venoms produced by animals for hunting of self-defence are rich in bioactive compounds with broad spectrum of biological activity. The papers presents the most promising compounds isolated from venoms of snakes, scorpions and toads. For these compounds both: mechanism of anticancer activity as well as possibilities of clinical use are presented.

  16. Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites

    OpenAIRE

    Xiao-Jia Chen; Xiao-Jing Zhang; Yan-Mei Shui; Jian-Bo Wan; Jian-Li Gao

    2016-01-01

    Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidat...

  17. A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery

    OpenAIRE

    Yuanfeng Ye; Xiaohong Hu

    2016-01-01

    According to previous reports, low pH-triggered nanoparticles were considered to be excellent carriers for anticancer drug delivery, for the reason that they could trigger encapsulated drug release at mild acid environment of tumor. Herein, an acid-sensitive β-cyclodextrin derivative, namely, acetalated-β-cyclodextrin (Ac-β-CD), was synthesized by acetonation and fabricated to nanoparticles through single oil-in-water (o/w) emulsion technique. At the same time, camptothecin (CPT), a hydrophob...

  18. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU

    2009-01-01

    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  19. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry)

    OpenAIRE

    Tiejun Zhao; Qiang Sun; Maud Marques; Michael Witcher

    2015-01-01

    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Ph...

  20. Arene ruthenium complexes as anticancer agents

    OpenAIRE

    Süss-Fink, Georg

    2012-01-01

    Neutral or cationic arene ruthenium complexes providing both hydrophilic as well as hydrophobic properties due to the robustness of the ruthenium–arene unit hold a high potential for the development of metal-based anticancer drugs. Mononuclear arene ruthenium complexes containing P- or N-donor ligands or N,N-, N,O- or O,O-chelating ligands, dinuclear arene ruthenium systems with adjustable organic linkers, trinuclear arene ruthenium clusters containing an oxo cap, tetranuclear arene ruthenium...

  1. Therapeutic aptamers: developmental potential as anticancer drugs

    OpenAIRE

    Lee, Ji Won; Kim, Hyun Jung; Heo, Kyun

    2015-01-01

    Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a seco...

  2. Optimization of personalized therapies for anticancer treatment

    OpenAIRE

    Vazquez, Alexei

    2013-01-01

    Background As today, there are hundreds of targeted therapies for the treatment of cancer, many of which have companion biomarkers that are in use to inform treatment decisions. If we would consider this whole arsenal of targeted therapies as a treatment option for every patient, very soon we will reach a scenario where each patient is positive for several markers suggesting their treatment with several targeted therapies. Given the documented side effects of anticancer drugs, it is clear tha...

  3. From antimicrobial to anticancer peptides. A review.

    OpenAIRE

    Diana eGaspar; A. Salomé eVeiga; Miguel A.R.B. eCastanho

    2013-01-01

    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs) in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective...

  4. Some medicinal plants as natural anticancer agents

    OpenAIRE

    Govind Pandey; S Madhuri

    2009-01-01

    India is the largest producer of medicinal plants and is rightly called the "Botanical garden of the World". The medicinal plants, besides having natural therapeutic values against various diseases, also provide high quality of food and raw materials for livelihood. Considerable works have been done on these plants to treat cancer, and some plant products have been marketed as anticancer drugs, based on the traditional uses and scientific reports. These plants may promote host resistance agai...

  5. Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants

    OpenAIRE

    Sirikantaramas, Supaart; Yamazaki, Mami; Saito, Kazuki

    2008-01-01

    Plants produce a variety of toxic compounds, which are often used as anticancer drugs. The self-resistance mechanism to these toxic metabolites in the producing plants, however, remains unclear. The plant-derived anticancer alkaloid camptothecin (CPT) induces cell death by targeting DNA topoisomerase I (Top1), the enzyme that catalyzes changes in DNA topology. We found that CPT-producing plants, including Camptotheca acuminata, Ophiorrhiza pumila, and Ophiorrhiza liukiuensis, have Top1s with ...

  6. A REVIEW: HERBS USED AS ANTICANCER AGENTS

    Directory of Open Access Journals (Sweden)

    Badri Nagarani

    2011-01-01

    Full Text Available Herbs are the plants which will have desirable odour, taste and other medical uses. Anti-cancer agents are effective in cancer treatment. Here an attempt has been made to review some herbs used for the prevention and treatment of cancer. These herbs were found for posses anticancer, cytotoxic or antioxidant activity in various pre-clinical or clinical studies. Cancer is a disease in which body cells become abnormal and divide without control. Cancer cell may invade nearby tissues and they may spread through the blood stream & lymphatic system to other parts of the body. The search for anticancer agents from the plant sources alkaloids in earnest in the 1950s such as Vincristine, Vinblastine and the isolation of cytotoxic Podophyllotoxins will reduce white blood cell count and caused bone marrow depression in rats. Roots, leaves, stem, root, bark and fruity of the plant herbs are used in the treatment of cancer. The dietary antioxidants having anti carcinogenic property are in demand. Identification and characterization of these anti-carcinogens in the diet can be used for reducing the risk of human cancer. Tea (Camellia thea an evergreen plant contains antioxidants which prevent and repair cellular damage caused by reactive free radicals. Supervitamin drinks containing a combination of Hordeum vulgare, Medicago sativa and Spirulina enhances the activity of immune cells against cancer. Mentha species containing antioxidants prevent reocurrence of cancer.

  7. Phytochemistry and Anticancer Potential of Notoginseng.

    Science.gov (United States)

    Wang, Chong-Zhi; Anderson, Samantha; Yuan, Chun-Su

    2016-01-01

    Asian ginseng, American ginseng, and notoginseng are three major species in the ginseng family. Notoginseng is a Chinese herbal medicine with a long history of use in many Oriental countries. This botanical has a distinct ginsenoside profile compared to other ginseng herbs. As a saponin-rich plant, notoginseng could be a good candidate for cancer chemoprevention. However, to date, only relatively limited anticancer studies have been conducted on notoginseng. In this paper, after reviewing its anticancer data, phytochemical isolation and analysis of notoginseng is presented in comparison with Asian ginseng and American ginseng. Over 80 dammarane saponins have been isolated and elucidated from different plant parts of notoginseng, most of them belonging to protopanaxadiol or protopanaxatriol groups. The role of the enteric microbiome in mediating notoginseng metabolism, bioavailability, and pharmacological actions are discussed. Emphasis has been placed on the identification and isolation of enteric microbiome-generated notoginseng metabolites. Future investigations should provide key insights into notoginseng's bioactive metabolites as clinically valuable anticancer compounds. PMID:26916912

  8. Straightforward conversion of decoquinate into inexpensive tractable new derivatives with significant antimalarial activities.

    Science.gov (United States)

    Beteck, Richard M; Coertzen, Dina; Smit, Frans J; Birkholtz, Lyn-Marie; Haynes, Richard K; N'Da, David D

    2016-07-01

    As part of a programme aimed at identifying rational new triple drug combinations for treatment of malaria, tuberculosis and toxoplasmosis, we have selected quinolones as one component, given that selected examples exhibit exceptionally good activities against the causative pathogens of the foregoing diseases. The quinolone decoquinate (DQ), an old and inexpensive coccidiostat, displays anti-malarial activity in vitro against Plasmodium falciparum (Pf). However, because of its exceedingly poor solubility in water or organic solvents, development of DQ as a drug is problematical. We have therefore converted DQ in straightforward fashion into tractable new derivatives that display good activities in vitro against chloroquine-sensitive NF54 and multidrug-resistant K1 and W2 Pf, and relatively low toxicities against human fibroblast cells. The most active compound, the N-acetyl derivative 30, is 5-fold more active than DQ against NF54 and K1 and equipotent with DQ against W2. It possesses an activity profile against all strains comparable with that of the artemisinin derivative artesunate. Overall, this compound and the other accessible and active derivatives serve as an attractive template for development of new and economic lead quinolones. PMID:27210430

  9. Influence of the π-coordinated arene on the anticancer activity of ruthenium(II) carbohydrate organometallic complexes

    NARCIS (Netherlands)

    Hanif, Muhammad; Meier, Samuel M; Nazarov, Alexey A; Risse, Julie; Legin, Anton; Casini, Angela; Jakupec, Michael A; Keppler, Bernhard K; Hartinger, Christian G

    2013-01-01

    The synthesis and in vitro cytotoxicity of a series of Ru(II)(arene) complexes with carbohydrate-derived phosphite ligands and various arene co-ligands is described. The arene ligand has a strong influence on the in vitro anticancer activity of this series of compounds, which correlates fairly well

  10. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2016-09-01

    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  11. A series of novel 1D coordination polymers constructed from metal?quinolone complex fragments linked by aromatic dicarboxylate ligands

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Yan, Shi-Wei; Sun, Dian-Zhen; Chen, Hai-Yan; Wang, Xin; Yang, Juan; Ye, Zhong-Li; Yuan, Ruo; Wang, En-Bo

    2012-08-01

    Self-assembly of quinolones with metal salts in the presence of aromatic dicarboxylate ligands affords a series of novel 1D metal-quinolone complexes, namely [Mn(Hppa)(oba)]·3H2O (1), [Co(Hppa)(oba)]·3.25H2O (2), [Zn(Hppa)(sdba)]·1.5H2O (3), [Mn(Hcf)(bpda)(H2O)]·2H2O (4), [Mn(Hppa)2(bpdc)] (5) and [Mn(Hlome)2(bpdc)]·4H2O (6) (Hppa = Pipemidic acid, Hcf = ciprofloxacin, Hlome = lomefloxacin). The structures of compounds 1-3 consist of novel polymeric chains spanning two different directions, which display an intriguing 1D → 3D inclined polycatenation of supramolecular ladders. Compound 4 exhibits a chain compound formed from the interconnection of [Mn2(Hcf)2(μ-CO2)2] dimers with bpda ligands. Compounds 5 and 6 are similar chain compounds constructed from [Mn(Hppa)2] (or [Mn(Hlome)2]) fragments linked by bpdc ligands. The magnetic properties of 4 have been studied, which indicate the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compound 3 are discussed.

  12. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

    Directory of Open Access Journals (Sweden)

    Ivan Laponogov

    Full Text Available The 2.7 A crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo IV subunit A (ParC from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a 'closed' dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA, but distinct from the 'open' gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts.

  13. Molecular characterization of quinolone resistance mechanisms and extended-spectrum β-lactamase production in Escherichia coli isolated from dogs.

    Science.gov (United States)

    Meireles, D; Leite-Martins, L; Bessa, L J; Cunha, S; Fernandes, R; de Matos, A; Manaia, C M; Martins da Costa, P

    2015-08-01

    The increasing prevalence of antimicrobial resistances is now a worldwide problem. Investigating the mechanisms by which pets harboring resistant strains may receive and/or transfer resistance determinants is essential to better understanding how owners and pets can interact safely. Here, we characterized the genetic determinants conferring resistance to β-lactams and quinolones in 38 multidrug-resistant Escherichia coli isolated from fecal samples of dogs, through PCR and sequencing. The most frequent genotype included the β-lactamase groups TEM (n=5), and both TEM+CTX-M-1 (n=5). Within the CTX-M group, we identified the genes CTX-M-32, CTX-M-1, CTX-M-15, CTX-M-55/79, CTX-M-14 and CTX-M-2/44. Thirty isolates resistant to ciprofloxacin presented two mutations in the gyrA gene and one or two mutations in the parC gene. A mutation in gyrA (reported here for the first time), due to a transversion and transition (TCG→GTG) originating a substitution of a serine by a valine in position 83 was also detected. The plasmid-encoded quinolone resistance gene, qnrs1, was detected in three isolates. Dogs can be a reservoir of genetic determinants conferring antimicrobial resistance and thus may play an important role in the spread of antimicrobial resistance to humans and other co-habitant animals.

  14. Identification of the main quinolone resistance determinant in Campylobacter jejuni and Campylobacter coli by MAMA-DEG PCR.

    Science.gov (United States)

    Hormeño, Lorena; Palomo, Gonzalo; Ugarte-Ruiz, María; Porrero, M Concepción; Borge, Carmen; Vadillo, Santiago; Píriz, Segundo; Domínguez, Lucas; Campos, Maria J; Quesada, Alberto

    2016-03-01

    Among zoonotic diseases, campylobacteriosis stands out as the major bacterial infection producing human gastroenteritis. Antimicrobial therapy, only recommended in critical cases, is challenged by resistance mechanisms that should be unambiguously detected for achievement of effective treatments. Quinolone (ciprofloxacin) resistance of Campylobacter jejuni and Campylobacter coli, the 2 main Campylobacter detected in humans, is conferred by the mutation gyrA C-257-T, which can be genotyped by several methods that require a previous identification of the pathogen species to circumvent the sequence polymorphism of the gene. A multiplex PCR, based on degenerated oligonucleotides, has been designed for unambiguous identification of the quinolone resistance determinant in Campylobacter spp. isolates. The method was verified with 249 Campylobacter strains isolated from humans (141 isolates) and from the 3 most important animal sources for this zoonosis: poultry (34 isolates), swine (38 isolates), and cattle (36 isolates). High resistance to ciprofloxacin, MIC above 4μg/mL, linked to the mutated genotype predicted by MAMA-DEG PCR (mismatch amplification mutation assay PCR with degenerated primers) was found frequently among isolates from the different hosts. PMID:26658311

  15. Environment-sensitive quinolone demonstrating long-lived fluorescence and unusually slow excited-state intramolecular proton transfer kinetics

    Science.gov (United States)

    Zamotaiev, O. M.; Shvadchak, V.; Sych, T. P.; Melnychuk, N. A.; Yushchenko, D.; Mely, Y.; Pivovarenko, V. G.

    2016-09-01

    A new small fluorescent dye based on 3-hydroxybenzo[g]quinolone, a benzo-analogue of Pseudomonas quinolone signal species, has been synthesized. The dye demonstrates interesting optical properties, with absorption in the visible region, two band emission due to an excited-state intramolecular proton transfer (ESIPT) reaction and high fluorescence quantum yield in both protic and aprotic media. Time-resolved fluorescence spectroscopy shows that the ESIPT reaction time is unusually long (up to 8 ns), indicating that both forward and backward ESIPT reactions are very slow in comparison to other 3-hydroxyquinolones. In spite of these slow rate constants, the ESIPT reaction was found to show a reversible character as a result of the very long lifetimes of both N* and T* forms (up to 16 ns). The ESIPT reaction rate is mainly controlled by the hydrogen bond donor ability in protic solvents and the polarity in aprotic solvents. Using large unilamellar vesicles and giant unilamellar vesicles of different lipid compositions, the probe was shown to preferentially label liquid disordered phases.

  16. Identification of the main quinolone resistance determinant in Campylobacter jejuni and Campylobacter coli by MAMA-DEG PCR.

    Science.gov (United States)

    Hormeño, Lorena; Palomo, Gonzalo; Ugarte-Ruiz, María; Porrero, M Concepción; Borge, Carmen; Vadillo, Santiago; Píriz, Segundo; Domínguez, Lucas; Campos, Maria J; Quesada, Alberto

    2016-03-01

    Among zoonotic diseases, campylobacteriosis stands out as the major bacterial infection producing human gastroenteritis. Antimicrobial therapy, only recommended in critical cases, is challenged by resistance mechanisms that should be unambiguously detected for achievement of effective treatments. Quinolone (ciprofloxacin) resistance of Campylobacter jejuni and Campylobacter coli, the 2 main Campylobacter detected in humans, is conferred by the mutation gyrA C-257-T, which can be genotyped by several methods that require a previous identification of the pathogen species to circumvent the sequence polymorphism of the gene. A multiplex PCR, based on degenerated oligonucleotides, has been designed for unambiguous identification of the quinolone resistance determinant in Campylobacter spp. isolates. The method was verified with 249 Campylobacter strains isolated from humans (141 isolates) and from the 3 most important animal sources for this zoonosis: poultry (34 isolates), swine (38 isolates), and cattle (36 isolates). High resistance to ciprofloxacin, MIC above 4μg/mL, linked to the mutated genotype predicted by MAMA-DEG PCR (mismatch amplification mutation assay PCR with degenerated primers) was found frequently among isolates from the different hosts.

  17. Molecular characterization of quinolone resistance mechanisms and extended-spectrum β-lactamase production in Escherichia coli isolated from dogs.

    Science.gov (United States)

    Meireles, D; Leite-Martins, L; Bessa, L J; Cunha, S; Fernandes, R; de Matos, A; Manaia, C M; Martins da Costa, P

    2015-08-01

    The increasing prevalence of antimicrobial resistances is now a worldwide problem. Investigating the mechanisms by which pets harboring resistant strains may receive and/or transfer resistance determinants is essential to better understanding how owners and pets can interact safely. Here, we characterized the genetic determinants conferring resistance to β-lactams and quinolones in 38 multidrug-resistant Escherichia coli isolated from fecal samples of dogs, through PCR and sequencing. The most frequent genotype included the β-lactamase groups TEM (n=5), and both TEM+CTX-M-1 (n=5). Within the CTX-M group, we identified the genes CTX-M-32, CTX-M-1, CTX-M-15, CTX-M-55/79, CTX-M-14 and CTX-M-2/44. Thirty isolates resistant to ciprofloxacin presented two mutations in the gyrA gene and one or two mutations in the parC gene. A mutation in gyrA (reported here for the first time), due to a transversion and transition (TCG→GTG) originating a substitution of a serine by a valine in position 83 was also detected. The plasmid-encoded quinolone resistance gene, qnrs1, was detected in three isolates. Dogs can be a reservoir of genetic determinants conferring antimicrobial resistance and thus may play an important role in the spread of antimicrobial resistance to humans and other co-habitant animals. PMID:25999092

  18. CancerHSP: anticancer herbs database of systems pharmacology

    Science.gov (United States)

    Tao, Weiyang; Li, Bohui; Gao, Shuo; Bai, Yaofei; Shar, Piar Ali; Zhang, Wenjuan; Guo, Zihu; Sun, Ke; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Mu, Jiexin; Pei, Tianli; Wang, Yuan; Li, Yan; Wang, Yonghua

    2015-06-01

    The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at http://lsp.nwsuaf.edu.cn/CancerHSP.php.

  19. Analysis of 155 reports of ADR Induced by Quinolones%155例喹诺酮类药品不良反应分析

    Institute of Scientific and Technical Information of China (English)

    钟晗; 刘晓琰; 崔敏; 苏颖杰

    2013-01-01

    目的 研究喹诺酮类药物在临床治疗中发生的不良反应(ADR)情况,寻找应对该类药物ADR的临床策略.方法 采用回顾性研究方法,对我院2004~2011年上报的喹诺酮类药物ADR进行系统分析.结果 155例ADR报表中涉及9种喹诺酮类药物,左氧氟沙星ADR例次最多(105例次).主要不良反应表现为过敏反应(40.4%)和消化系统症状(27.1%).结论 对喹诺酮类药物的临床应用需加强监测,促进合理用药.%Objective To determine adverse drug reaction (ADR) occurrence associated with quinolones in clinical practices. Methods 155 reports of quinolones-induced ADR from 2010 to 2011 were analyzed. Results Nine drugs of quinolones were involved in 155 ADR reports, among which levofloxacin resulted in ADR most frequently(105 cases). The ADRs manifestations mainly covered allergies(40.4%) and digestive system disease symptoms(27.1%). Conclusion It is necessary to monitor clinical application of quinolones, therefore promote rational use of drug.

  20. Research progress on the metal complexes of quinolone drug ligands%喹诺酮类药物金属配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    Objective The article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes, in order to provide a foundation for further research. Methods The ralated literatures were summarized. Results The development of the research of the quinolone drug metal complexes is fast,but exists many questions. Conclusion Some suggestions of the in-depth research of the quinolone drug metal complexes are presented.%目的 对喹诺酮类药物的发展过程及其金属配合物的配位结构和活性等方面进行综述,为进一步研究喹诺酮类药物金属配合物提供科学依据.方法 对相关文献进行归纳、总结和综述.结果 喹诺酮类药物金属配合物的研究取得较快发展,但还存在着许多有待解决的问题.结论 展望了喹诺酮类药物金属配合物研究的发展趋势.

  1. 沙眼衣原体对喹诺酮类耐药机制的进展%Update on the mechanism of Chlamydia trachomatis resistance to quinolones

    Institute of Scientific and Technical Information of China (English)

    杨晓静; 刘全忠

    2009-01-01

    Quinolones are commonly used to treat Chlamydiatra chomatis inection in clinic at present.However,the resistance of Chlamydia trachomatis to quinolones has been increasingly reported.It has becn shown that the resistance is related to point mutations in the quinolone-resistance-determinning region of DNA gyrase gene and topoisomerase IV subunit genes.These mutations are located most commonly at Ser-83,less frequently at Asp-87.There are also some other mechanisms underlying the resistance.Further studies are needed for the elucidation of exact mechanism of Chlamydia trachomatis resistance to quinolones.%喹诺酮类药物目前在临床上常用于治疗沙眼衣原体感染,但近年来有关沙眼衣原体对其耐药的报道不断出现.研究发现,喹诺酮类耐药的产生与DNA回旋酶和拓扑异构酶Ⅳ亚单位基因的喹诺酮耐药决定区域的点突变有关.最常见的突变位于Ser-83,少数情况下位于Asp-87,还有一些其他可能的耐药机制.沙眼衣原体对喹诺酮类耐药的确切机制尚待进一步研究.

  2. Clinical application of a ligation-independent pathway of multiplex ligation-dependent probe amplification for the determination of quinolone susceptibility of Streptococcus pneumoniae.

    Science.gov (United States)

    Uno, Naoki; Araki, Nobuko; Kaku, Norihito; Kosai, Kosuke; Hasegawa, Hiroo; Yanagihara, Katsunori

    2016-09-01

    We previously uncovered a ligation-independent pathway of multiplex ligation-dependent probe amplification (MLPA) through which products of MLPA could be amplified without both hybridization and ligation reactions. Here, we utilized this pathway to detect an antibiotic resistance mutation of quinolones in Streptococcus pneumoniae. PMID:27343683

  3. 喹诺酮类药物的严重不良反应及合理应用%Serious ADRs of Quinolones and TheirRational Use

    Institute of Scientific and Technical Information of China (English)

    付铁梅; 田丽娟

    2011-01-01

    目的 促进喹诺酮类药物的合理使用,减少药品不良反应和耐药性的发生.方法 通过查阅文献等,对喹诺酮类药物的严重不良反应及产生原因进行分析,并提出合理使用的对策建议.结果 与结论随着喹诺酮类药物临床使用量不断增加,其严重药品不良反应的发生也越来越多.临床用药,一定要增强合理用药意识,确保患者用药安全有效.%Objective To promote the rational use of quinolones to reduce serious adverse drug reactions (ADRs) and occurrence of resistance to qmnolones. Methods The literature review was conducted to analyze the serious ADRs of quinolones and their causes, and the countermeasures of their rational use were proposed. Results and Conclusion As the clinical use of quinolones increasing, serious ADRs occur more and more, Both doctors and patients should enhance Erie awareness of rational use of quinolones to reduce the serious ADRs and ensure lhe safe and effective drug use m patients.

  4. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

    DEFF Research Database (Denmark)

    McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.;

    2011-01-01

    Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds contai...

  5. Reactions and interactions in handling anticancer drugs.

    Science.gov (United States)

    D'Arcy, P F

    1983-01-01

    The clinical toxicity of anticancer drugs has been well documented with regard to the adverse effects of treatment in patients. However, many of these drugs have a direct irritant effect on the skin, eyes, mucous membranes, and other tissues. Handled without due care, especially when being prepared for injection, most cytotoxic drugs can cause local toxic or allergic reactions; they also present hazards of carcinogenicity and mutagenicity. This spectrum of potential risk should be kept in mind by personnel administering or handling these drugs, especially in oncology units where just a few individuals may routinely and frequently reconstitute many doses of cytotoxic agents. This is work in which the hospital pharmacist should and must be involved; indeed, many of the techniques and skills required are identical with those used in standard aseptic procedures for preparing pharmaceutical products. Pharmacy departments should take the initiative in making hospital staff aware of the potential risks of handling neoplastic agents, and they should spearhead a multidisciplinary assessment for producing local guidelines for working with these drugs. This article warns practitioners about the inherent dangers of these practitioner-drug interactions and suggests ways in which they may be reduced. Information is given in tabular form regarding recommended procedures for reconstituting 24 anticancer drugs and precautions to protect the personnel handling them, especially when there is spillage of powdered or liquid drugs. Also, guidelines are given about incompatibilities with admixtures of such drugs, and the literature is reviewed relative to recent developments in hospital pharmacy departments where reconstitution of anticancer drugs has been incorporated into existing intravenous fluid preparation/admixture units. Not only has this been shown to be safer and more effective in terms of time and labor, but also it has cut the cost of injectable cytotoxic drugs by an

  6. 我院门诊喹诺酮类药物临床应用调查%Investigation on Clinical Use of Quinolones in Outpatient Clinic

    Institute of Scientific and Technical Information of China (English)

    田雪莉; 周霞

    2011-01-01

    Objective To understand the use status of quinolone- related drugs in the outpatient clinic for standardizing rational drug use in clinic. Methods The prescriptions involving quinolone- related drugs in the outpatient clinic were extracted and statistically analyzed in aspects of disease category, age, drug variety and rationality of drug use. Results Quinolone medication accounted for 21.50% of all antibiotic uses in the outpatient clinic. 43.06% of quinolones were used for respiratory diseases. Among them, levofloxacin had the highest use frequency(48.79% ). Unreasonable prescriptions included the use of quinolones for the patients yomger than 18 years old and without clear diagnosis of infectious diseases. Conclusion Quinolones are commonly used in anti- infection treatment in the outpatient clinic. The use indicators are rationally grasped as a whole. But using quinolones in children still exists, which should be needed to pay attention. The dosage in different ages has no apparent difference. The medieation dose in elderly patients should be adjusted.%目的 了解医院门诊喹诺酮类药物的使用情况,规范临床合理用药.方法 抽取喹诺酮类药物的处方,从痛种、患者年龄、用药品种、用药合理性等方面进行统计分析.结果 喹诺酮类药物的使用占全部抗茵药物的21.50%,43.06%用于呼吸系统疾病,其中左氧氟沙星使用频率最高(占喹诺酮类的48.79%).不合理用药包括18岁以下儿童用药、无感染性疾病诊断用药等.结论 喹诺酮类药物在医院门诊抗感染治疗中比较常见,应用指征掌握基本合理,但仍存在儿童用药,应予以重视.不同年龄用量差异不明显,对老年患者用药应进行剂量调整.

  7. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K

    2013-02-01

    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

  8. Diaryl Urea: A Privileged Structure in Anticancer Agents.

    Science.gov (United States)

    Garuti, Laura; Roberti, Marinella; Bottegoni, Giovanni; Ferraro, Mariarosaria

    2016-01-01

    The diaryl urea is an important fragment/pharmacophore in constructing anticancer molecules due to its near-perfect binding with certain acceptors. The urea NH moiety is a favorable hydrogen bond donor, while the urea oxygen atom is regarded as an excellent acceptor. Many novel compounds have been synthesized and evaluated for their antitumor activity with the successful development of sorafenib. Moreover, this structure is used to link alkylating pharmacophores with high affinity DNA binders. In addition, the diaryl urea is present in several kinase inhibitors, such as RAF, KDR and Aurora kinases. Above all, this moiety is used in the type II inhibitors: it usually forms one or two hydrogen bonds with a conserved glutamic acid and one with the backbone amide of the aspartic acid in the DFG motif. In addition, some diaryl urea derivatives act as Hedgehog (Hh) ligands, binding and inhibiting proteins involved in the homonymous Hh signaling pathway. In this review we provide some of the methodologies adopted for the synthesis of diaryl ureas and a description of the most representative antitumor agents bearing the diaryl urea moiety, focusing on their mechanisms bound to the receptors and structure-activity relationships (SAR). An increased knowledge of these derivatives could prompt the search to find new and more potent compounds. PMID:27063259

  9. Hydroxamic acid - A novel molecule for anticancer therapy

    Directory of Open Access Journals (Sweden)

    Dilipkumar Pal

    2012-01-01

    Full Text Available Hydroxamic acid is a potent moiety not only in the field of cancer therapy but also as a mutagenic agent. Among the various derivatives of hydroxamic acid, SAHA (Suberoylanilide Hydroxamic Acid is considered as a potent anticancer agent. Scientists from the different corner synthesized different hydroxamic acid moieties with some straight chain oxazole, thiadiazole, biphenyl moieties in the terminal position. Acetylation and deacetylation of histones of the core proteins of nucleosomes in chromatin play an important role in the regulation of gene expression. The level of acetylation of histones is established and maintained by two classes of enzymes, histone acetyltransferase and histone deacetylases, which have been identified as transcriptional coactivators and transcriptional corepressors, respectively. There is increasing evidence that aberrant histone acetylation has been linked to various malignant diseases. Great efforts are currently underway for the design of more potent and less toxic candidates for the treatment of cancer. In recent years, hydroxamic acid derivatives have attracted increasing attention for their potential as highly efficacious in combating various etiological factors associated with cancer. Our main intention to draw an attention is that this single functional moiety has not only fit in the receptor but also create a diversified activity.

  10. ANTICANCER ACTIVITY OF ISOLATED CHEMICAL CONSTITUENTS FROM MILIUSA SMITHIAE

    Directory of Open Access Journals (Sweden)

    Chonthicha Naphong

    2013-01-01

    Full Text Available Miliusa plants belonging to the family Annonaceae are found in Thailand and have been used as Thai traditional medicines. There have been a few previously reports on the chemical constituents of plants in this genus, describing the presence of aporphine alkaloids, terpenoids, flavonoids, phenylpropanoids, styrylpyrones, bis-styryls and homogentisic acid derivatives. Miliusa smithiae, a new species for Thailand and world, has not been studied chemical composition. The present study described phytochemical study of the leaves and twigs of M. smithiae together with their cytotoxicity. The M. smithiae was selected and percolated with hexane, ethyl acetate, acetone and methanol. The extracts were purified and elucidated chemical structures. The constituent of ethyl acetate extract of M. smithiae has been investigated. We isolated and identified two flavonoid derivatives, 5-hydroxy-3,7,4′-trimetoxyflavone (1 and 5,3′-dihydroxy-3,7,4′-trimetoxyflavone (2. The structures of these compounds were elucidated on the basis of spectroscopic evidence. Studies on ethyl acetate extract of M. smithiae has now resulted the isolation and structural characterization of two flavonoids. Their anticancer activities were evaluated using SRB assays. In this method, compound 2 showed potential activity in cell lines.

  11. Secondary metabolites as DNA topoisomerase inhibitors: A new era towards designing of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Supriya Baikar

    2010-01-01

    Full Text Available A large number of secondary metabolites like alkaloids, terpenoids, polyphenols and quinones are produced by the plants. These metabolites can be utilized as natural medicines for the reason that they inhibit the activity of DNA topoisomerase which are the clinical targets for anticancer drugs. DNA topoisomerases are the cellular enzymes that change the topological state of DNA through the breaking and rejoining of DNA strands. Synthetic drugs as inhibitors of topoisomerases have been developed and used in the clinical trials but severe side effects are a serious problem for them therefore, there is a need for the development of novel plant-derived natural drugs and their analogs which may serve as appropriate inhibitors with respect to drug designing. The theme for this review is how secondary metabolites or natural products inactivate the action of DNA topoisomerases and open new avenues towards isolation and characterization of compounds for the development of novel drugs with anticancer potential.

  12. Anticancer and antioxidant activities of the peptide fraction from algae protein waste.

    Science.gov (United States)

    Sheih, I-Chuan; Fang, Tony J; Wu, Tung-Kung; Lin, Peng-Hsiang

    2010-01-27

    Algae protein waste is a byproduct during production of algae essence from Chlorella vulgaris. There is no known report on the anticancer peptides derived from the microalgae protein waste. In this paper, the peptide fraction isolated from pepsin hydrolysate of algae protein waste had strong dose-dependent antiproliferation and induced a post-G1 cell cycle arrest in AGS cells; however, no cytotoxicity was observed in WI-38 lung fibroblasts cells in vitro. The peptide fraction also revealed much better antioxidant activity toward peroxyl radicals and LDL than those of Trolox. Among these peptides, a potent antiproliferative, antioxidant, and NO-production-inhibiting hendecapeptide was isolated, and its amino acid sequence was VECYGPNRPQF. These results demonstrate that inexpensive algae protein waste could be a new alternative to produce anticancer peptides. PMID:19916544

  13. Discovery and development of natural product oridonin-inspired anticancer agents.

    Science.gov (United States)

    Ding, Ye; Ding, Chunyong; Ye, Na; Liu, Zhiqing; Wold, Eric A; Chen, Haiying; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2016-10-21

    Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic. PMID:27344488

  14. A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis

    Directory of Open Access Journals (Sweden)

    Ye Xinyu

    2010-10-01

    Full Text Available Abstract Background The first report on the transferable, plasmid-mediated quinolone-resistance determinant qnrA1 was in 1998. Since then, qnr alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural arrangement. Results We conducted random and site-directed mutagenesis on qnrA1 and on qnrC, a newly identified quinolone-resistance gene from Proteus mirabilis. Many of the Qnr mutants lost their quinolone resistance function. The highly conserved hydrophobic Leu or Phe residues at the center of the pentapeptide repeats are known as i sites, and loss-of-function mutations included replacement of the i site hydrophobic residues with charged residues, replacing the i-2 site, N-terminal to the i residues, with bulky side-chain residues, introducing Pro into the β-helix coil, deletion of the N- and C-termini, and excision of a central coil. Molecular dynamics simulations and homology modeling demonstrated that QnrC overall adopts a stable β-helix fold and shares more similarities with MfpA than with other PRP structures. Based on homology modeling and molecular dynamics simulation, the dysfunctional point mutations introduced structural deformations into the quadrilateral β-helix structure of PRPs. Of the pentapeptides of QnrC, two-thirds adopted a type II β-turn, while the rest adopted type IV turns. A gap exists between coil 2 and coil 3 in the QnrC model structure, introducing a structural flexibility that is similar to that seen in MfpA. Conclusion The hydrophobic core and the β-helix backbone conformation are important for maintaining the quinolone resistance property of Qnr proteins. QnrC may share structural similarity with MfpA.

  15. Research progress on the metal complexes of quinolone drug ligands%金属与喹诺酮类药物构筑的配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    This article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes. Some suggestions of the quinolone drug metal complexes in-depth in the future were presented.%本文综述了喹诺酮类药物的发展过程,以及各种金属离子与该类药物构筑形成配合物晶体结构方面的研究进展,展望了此类研究的发展趋势.

  16. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  17. Enediyne compounds - new promises in anticancer therapy.

    Science.gov (United States)

    Gredicak, Matija; Jerić, Ivanka

    2007-06-01

    Scientists of all kinds have long been intrigued by the nature, action and potential of natural toxins that possess exceptional antibacterial and anticancer activities. These compounds, named enediynes, are among the most effective chemotherapeutic agents known. Often compared with intelligent weapons, due to the unique structure and sophisticated mechanism by which they destroy double-helical DNA, enediyne antibiotics are nowadays the most promising leaders in the anticancer therapy. Apart from their diversity, enediyne compounds share some structural and functional similarities. One fragment of a structure is responsible for the recognition and transport, another part acts as molecular trigger while the third, reactive enediyne unit, undergoes Bergman cycloaromatization and causes DNA breakage. Members of the enediyne family are already in clinical use to treat various cancers, but more general use is limited by their complex structure, which makes them formidable targets for synthetic chemists. There are three main approaches in the design of new enediyne-related compounds: improvement of enediyne >warheadsenediynes, their mode of action and efforts undertaken to design artificial enediyne-related DNA cleaving agents. PMID:17507311

  18. In vivo anticancer activity of vanillin semicarbazone

    Institute of Scientific and Technical Information of China (English)

    Shaikh M Mohsin Ali; M Abul Kalam Azad; Mele Jesmin; Shamim Ahsan; M Mijanur Rahman; Jahan Ara Khanam; M Nazrul Islam; Sha M Shahan Shahriar

    2012-01-01

    Objective:To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods:The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results:Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions: It can be concluded that VSC can therefore be considered as potent anticancer agent.

  19. Anticancer activities of Nigella sativa (black cumin).

    Science.gov (United States)

    Khan, Md Asaduzzaman; Chen, Han-chun; Tania, Mousumi; Zhang, Dian-zheng

    2011-01-01

    Nigella sativa has been used as traditional medicine for centuries. The crude oil and thymoquinone (TQ) extracted from its seeds and oil are effective against many diseases like cancer, cardiovascular complications, diabetes, asthma, kidney disease etc. It is effective against cancer in blood system, lung, kidney, liver, prostate, breast, cervix, skin with much safety. The molecular mechanisms behind its anticancer role is still not clearly understood, however, some studies showed that TQ has antioxidant role and improves body's defense system, induces apoptosis and controls Akt pathway. Although the anti-cancer activity of N. sativa components was recognized thousands of years ago but proper scientific research with this important traditional medicine is a history of last 2∼3 decades. There are not so many research works done with this important traditional medicine and very few reports exist in the scientific database. In this article, we have summarized the actions of TQ and crude oil of N. sativa against different cancers with their molecular mechanisms. PMID:22754079

  20. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  1. ATP-triggered anticancer drug delivery

    Science.gov (United States)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  2. Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity.

    Science.gov (United States)

    Tao, Li; Wang, Sheng; Zhao, Yang; Sheng, Xiaobo; Wang, Aiyun; Zheng, Shizhong; Lu, Yin

    2014-09-25

    Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [d-(+)-β-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. PMID:24916702

  3. Polymeric micelles in anticancer therapy : targeting, imaging and triggered release

    NARCIS (Netherlands)

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J Frank W; Hennink, Wim E

    2010-01-01

    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  4. Preclinical pharmacodynamic evaluation of antibiotic nitroxoline for anticancer drug repurposing

    OpenAIRE

    Zhang, Qi; Wang, Shanshan; Yang, Dexuan; PAN, KEVIN; Li, Linna; Yuan, Shoujun

    2016-01-01

    The established urinary antibiotic nitroxoline has recently regained considerable attention, due to its potent activities in inhibiting angiogenesis, inducing apoptosis and blocking cancer cell invasion. These features make nitroxoline an excellent candidate for anticancer drug repurposing. To rapidly advance nitroxoline repurposing into clinical trials, the present study performed systemic preclinical pharmacodynamic evaluation of its anticancer activity, including a methyl thiazolyl tetrazo...

  5. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that fi

  6. Adsorption of quinolone antibiotics in spherical mesoporous silica: Effects of the retained template and its alkyl chain length.

    Science.gov (United States)

    Liang, Zhijie; Zhaob, Zhiwei; Sun, Tianyi; Shi, Wenxin; Cui, Fuyi

    2016-03-15

    In this study, mesoporous silica (meso-silica) MCM-41 and those with the templates retained were synthesized and characterized. Adsorption capacities of the synthesized materials towards typical quinolone antibiotic pollutants, enrofloxacin and norfloxacin as representative, were investigated, and effects of the alkyl chain length of the templates on the adsorption capacity were evaluated. The results of this study indicated that the retained templates enhanced the adsorption capacities (Qmax) of the meso-silica MCM-41 toward hydrophobic enrofloxacin, but had an inhibitory effect on that towards hydrophilic norfloxacin, which were attributed to the hydrophobic inter-environment created by the long alkyl chains of the retained templates. Importantly, the adsorption capacity increased with the increase of the alkyl chain length of the retained templates. PMID:26642441

  7. Optimal control of ultrafast laser driven many-electron dynamics in a polyatomic molecule: N-methyl-6-quinolone

    Science.gov (United States)

    Klamroth, Tillmann

    2006-04-01

    We report time-dependent configuration interaction singles calculations for the ultrafast laser driven many-electron dynamics in a polyatomic molecule, N-methyl-6-quinolone. We employ optimal control theory to achieve a nearly state-selective excitation from the S0 to the S1 state, on a time scale of a few (≈6) femtoseconds. The optimal control scheme is shown to correct for effects opposing a state-selective transition, such as multiphoton transitions and other, nonlinear phenomena, which are induced by the ultrashort and intense laser fields. In contrast, simple two-level π pulses are not effective in state-selective excitations when very short pulses are used. Also, the dependence of multiphoton and nonlinear effects on the number of states included in the dynamical simulations is investigated.

  8. Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae.

    Science.gov (United States)

    Bernard, J; Armand-Lefèvre, L; Luce, E; El Mniai, A; Chau, F; Casalino, E; Andremont, A; Ruppé, E

    2016-07-01

    Emergence of resistant Enterobacteriaceae in the intestinal microbiota during antibiotic treatment is well documented but its early dynamic is not. Here, we compared the densities of total Enterobacteriaceae and relative abundance (RA) of quinolone-resistant Enterobacteriaceae (QRE) in the first stool passed by patients who had a short exposure to levofloxacin (levofloxacin, n=12) or not (control, n=8). Mean densities (SD) (log CFU/g stool) of total Enterobacteriaceae were lower in the levofloxacin group than in the control group-3.4 (1.6) versus 6.7 (1.7), respectively, p levofloxacin group than in the control group-49.7% (23.4) versus 0.1% (3.2), respectively, p levofloxacin has a profound impact on the densities of total Enterobacteriaceae and the QRE-RA. PMID:27126608

  9. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

    KAUST Repository

    Bräuer, Alois

    2015-11-10

    © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

  10. Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents.

    Science.gov (United States)

    Zhang, Ling; Addla, Dinesh; Ponmani, Jeyakkumar; Wang, Ao; Xie, Dan; Wang, Ya-Nan; Zhang, Shao-Lin; Geng, Rong-Xia; Cai, Gui-Xin; Li, Shuo; Zhou, Cheng-He

    2016-03-23

    A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.

  11. Shyntesis and cytotoxicity evaluation in vitro of new compounds with hybrid structures of 8-flavoneacetic acid and quinolones; Sintesis y evaluacion citotoxica in vitro de nuevos compuestos con estructuras hibridas del acido 8-flavonacetico quinolonas

    Energy Technology Data Exchange (ETDEWEB)

    Biaa, M.F.; Castellano, J.M.; Emling, F.; Schlick, E. [Knoll, S.a., Madrid (Spain)

    1994-12-31

    Using the structural similarity between 8-flavoneacetic acid the antitumor quinolones, we have prepared some hybrid compounds on both systems and studied their cytotoxicity. None of the sinthesized compounds have shown sufficient interest for further development. 33 refs.

  12. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  13. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    In the first part of the thesis the work towards a new generation of liposomal drug delivery systems for anticancer agents is described. The drug delivery system takes advantage of the elevated level of secretory phospholipase A2 (sPLA2) IIA in many tumors and the enhanced permeability......-trans retinoic acid, α-tocopheryl succinate and calcitriol were examined for their ability to be incorporated into the investigated drug delivery system and syntheses of the phospholipid prodrugs are described. The majority of the phospholipid prodrugs were able to form particles with diameters close to 100 nm...... that upon sPLA2 triggering the formulated phospholipid prodrugs displayed IC50 values in range from 3–36 μM and complete cell death was observed when higher drug concentrations were applied. Promising for the drug delivery system the majority of the phospholipid prodrugs remain non-toxic in the absence...

  14. ANTICANCER HERBS IN AYURVEDA: A REVIEW

    Directory of Open Access Journals (Sweden)

    A.Vijaya Lakshmi

    2013-04-01

    Full Text Available Cells are the building blocks of living things. Normal cells multiply when the body needs them, and die when the body doesn't need them. Cancer is the uncontrolled growth of abnormal cells in the body. Cancer grows out of normal cells in the body. Cancer appears to occur when the growth of cells in the body is out of control and cells divide too quickly. In the present world of increased life span Cancers account for approximately 13% of all deaths each year. In 2008 approximately 12.7 million cancers were diagnosed and 7.6 million people died of cancer worldwide. There are many reasons for this like increased pollution, altered life style and increasing anxiety levels in the psychosomatic front. In Ayurveda there is mention of a condition similar to cancerous growths, their properties, types, signs and symptoms and treatments. This paper reviews the work done on anticancer properties of some of the herbs.

  15. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem A.

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  16. Utilization of Quinolones in Our Hospital from 2007 to 2009%我院2007-2009年喹诺酮类药应用分析

    Institute of Scientific and Technical Information of China (English)

    张桂芬; 支伟锋; 归莱; 谢丹

    2011-01-01

    OBJECTIVE: To evaluate the utilization and tendency of quinolones in our hospital. METHODS: Using DDD method, the utilization of quinolones in our hospital from 2007 to 2009 were analyzed statistically in terms of drug variety, consumption sum, DDDs and DDC, etc. RESULTS: The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Lomefloxacin tablets,Gatifloxacin capsules and Levofloxacin tablets (domestic). The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection(domestic), Ciprofloxacin sodium chloride injection, Fleroxacin glucose injection. CONCLUSION: The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.%目的:评价我院喹诺酮类药的应用现状及趋势.方法:采用限定日剂量方法,对我院2007-2009年喹诺酮类药的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析.结果:喹诺酮类药销售金额在抗菌药物中所占比例逐年下降.3年来,在口服喹诺酮类药中,销售金额、DDDs排序列前3位的依次是洛美沙星片、加替沙星胶囊、左氧氟沙星片(国产);在注射喹诺酮类药中,销售金额、DDDs排序列前4位的均有左氧氟沙星注射液(国产)、环丙沙星氯化钠注射液、氟罗沙星葡萄糖注射液.结论:我院喹诺酮类药应用基本合理,但仍应进一步加强其使用监管.

  17. Utilization of Quinolones in Our Hospital from 2009 to 2011%2009~2011年喹诺酮类药物应用分析

    Institute of Scientific and Technical Information of China (English)

    徐春燕

    2013-01-01

      目的探讨我院喹诺酮类药物的应用现状及趋势。方法采用限定日剂量方法,对我院2009~2011年喹诺酮类药物的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析。结果3年来,在口服喹诺酮类药物中,销售金额处于前三位的是加替沙星胶囊、左氧氟沙星胶囊、氟罗沙星胶囊;在注射喹诺酮类药物中,销售金额和DDDs排序列前四位的有盐酸左氧氟沙星注射液、加替沙星针、氟罗沙星针、依诺沙星注射液。结论我院喹诺酮类药物应用基本合理,但仍应进一步加强其使用监督管理。%Objective To evaluate the utilization and tendency of quinolones in our hospital. Methods Using DDD meth-od, the utilization of quinolones in our hospital from 2009 to 2011 were analyzed statistical y in terms of drug variety, consump-tion sum, DDDs and DDC, etc. Results The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Gatifloxacin capsules, Levofloxacin capsules and Fleroxacin capsules.The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection, Gatifloxacin injection, Fleroxacin injection, Enoxacin injection. Conclusion The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.

  18. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  19. CHIP buffers heterogeneous Bcl-2 expression levels to prevent augmentation of anticancer drug-resistant cell population.

    Science.gov (United States)

    Tsuchiya, M; Nakajima, Y; Waku, T; Hiyoshi, H; Morishita, T; Furumai, R; Hayashi, Y; Kishimoto, H; Kimura, K; Yanagisawa, J

    2015-08-27

    Many types of cancer display heterogeneity in various features, including gene expression and malignant potential. This heterogeneity is associated with drug resistance and cancer progression. Recent studies have shown that the expression of a major protein quality control ubiquitin ligase, carboxyl terminus of Hsc70-interacting protein (CHIP), is negatively correlated with breast cancer clinicopathological stages and poor overall survival. Here we show that CHIP acts as a capacitor of heterogeneous Bcl-2 expression levels and prevents an increase in the anticancer drug-resistant population in breast cancer cells. CHIP knockdown in breast cancer cells increased variation in Bcl-2 expression levels, an antiapoptotic protein, among the cells. Our results also showed that CHIP knockdown increased the proportion of anticancer drug-resistant cells. These findings suggest that CHIP buffers variation in gene expression levels, affecting resistance to anticancer drugs. In single-cell clones derived from breast cancer cell lines, CHIP knockdown did not alter the variation in Bcl-2 expression levels and the proportion of anticancer drug-resistant cells. In contrast, when clonal cells were treated with a mutagen, the variation in Bcl-2 expression levels and proportion of anticancer drug-resistant cells were altered by CHIP knockdown. These results suggest that CHIP masks genetic variations to suppress heterogeneous Bcl-2 expression levels and prevents augmentation of the anticancer drug-resistant population of breast cancer cells. Because genetic variation is a major driver of heterogeneity, our results suggest that the degree of heterogeneity in expression levels is decided by a balance between genetic variation and the buffering capacity of CHIP.

  20. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-01-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics. PMID:27476814

  1. Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard.

    Science.gov (United States)

    Tomšík, Pavel

    2014-06-01

    Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned. PMID:24123573

  2. Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard.

    Science.gov (United States)

    Tomšík, Pavel

    2014-06-01

    Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned.

  3. Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles

    Science.gov (United States)

    Pan-In, Porntip; Wanichwecharungruang, Supason; Hanes, Justin; Kim, Anthony J

    2014-01-01

    Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. PMID:25125977

  4. Synthesis, in vitro anticancer and antimicrobial evaluation of novel substituted dihydropyrimidines

    Directory of Open Access Journals (Sweden)

    K Rana

    2014-01-01

    Full Text Available A series of 1,4-dihydropyrimidine derivatives 3(a-t were prepared from Biginelli reactions by using ethyl acetoacetate, substituted benzaldehyde and thiourea in the presence of piperidine and ethanol. The compounds 3(a-t were reacted with dimethylsulphate, diethylsulphate, butyl bromide and benzyl chloride to give the new series of compounds 4(a-t. The structures of the newly synthesized compounds 4(a-t were established by IR, 1 H NMR, Mass spectra and elemental analysis. The synthesized compounds were evaluated for their in vitro anticancer activity by using Sulforhodamine B assay method against the growth of four humans cancer cell lines, antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and for antifungal activity against Candida albicans and Aspergillus niger. The compounds exhibited good anticancer activity and moderate antibacterial and antifungal activities. Compounds 4b, 4c, 4d, 4g, 4i, 4n, 4o, 4q and 4s showed significant anticancer activity when compared with the doxorubicin as a standard reference drug.

  5. Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Seyed

    2014-01-01

    Full Text Available The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2, a natural occurring styryl-lactone. Therefore, it includes (i the source of GTN and other metabolites; (ii isolation, purification, and (iii the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.

  6. A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Josinete B. Vieira

    2014-07-01

    Full Text Available The Density Functional Theory (DFT method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA and hierarchical cluster analysis (HCA were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS and principal component regression (PCR models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11 = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA, cellular permeability (PCaCO2, cell permeability Maden Darby Canine Kidney (PMDCK, skin permeability (PSkin, plasma protein binding (PPB and penetration of the blood-brain barrier (CBrain/Blood, and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

  7. 1,3,4-Thiadiazole Based Anticancer Agents.

    Science.gov (United States)

    Aliabadi, Alireza

    2016-01-01

    In recent years, researchers like medicinal chemists in the field of medicinal chemistry have widely utilized the 1,3,4-thiadiazole nucleus to investigate its biological and pharmacological effects. This heterocyclic structure has demonstrated various bioactivities such as antifungal, antimicrobial, antiviral, antileishmanial, anti-inflammatory, antihypertensive, antiepileptic, and anticancer effects among others. Anticancer activity is one of its promising effect as five membered heterocyclic rings have widely been investigated by researchers in the recent years. Herein, we reviewed the chemical structures bearing 1,3,4-thiadiazole template exerting anticancer activity. PMID:27484056

  8. Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.

    Science.gov (United States)

    Niu, Yu; Meng, Qiu-Xia

    2013-01-01

    This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation. PMID:23600735

  9. Anticancer Inhibitors of Hsp90 Function: Beyond the Usual Suspects.

    Science.gov (United States)

    Garg, Gaurav; Khandelwal, Anuj; Blagg, Brian S J

    2016-01-01

    The 90-kDa heat-shock protein (Hsp90) is a molecular chaperone responsible for the stability and function of a wide variety of client proteins that are critical for cell growth and survival. Many of these client proteins are frequently mutated and/or overexpressed in cancer cells and are therefore being actively pursued as individual therapeutic targets. Consequently, Hsp90 inhibition offers a promising strategy for simultaneous degradation of several anticancer targets. Currently, most Hsp90 inhibitors under clinical evaluation act by blocking the binding of ATP to the Hsp90 N-terminal domain and thereby, induce the degradation of many Hsp90-dependent oncoproteins. Although, they have shown some promising initial results, clinical challenges such as induction of the heat-shock response, retinopathy, and gastrointestinal tract toxicity are emerging from human trials, which constantly raise concerns about the future development of these inhibitors. Novobiocin derivatives, which do not bind the chaperone's N-terminal ATPase pocket, have emerged over the past decade as an alternative strategy to inhibit Hsp90, but to date, no derivative has been investigated in the clinical setting. In recent years, a number of natural or synthetic compounds have been identified that modulate Hsp90 function via various mechanisms. These compounds not only offer new chemotypes for the development of future Hsp90 inhibitors but can also serve as chemical probes to unravel the biology of Hsp90. This chapter presents a synopsis of inhibitors that directly, allosterically, or even indirectly alters Hsp90 function, and highlights their proposed mechanisms of action. PMID:26916001

  10. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Human Isolates in Iran

    Directory of Open Access Journals (Sweden)

    Ehsaneh Shams

    2015-01-01

    Full Text Available The purpose of this study was to determine the prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR genes (qnrA, qnrB, qnrS, aac(6′-Ib-cr, and qepA among ESBL-producing Klebsiella pneumoniae isolates in Kashan, Iran. A total of 185 K. pneumoniae isolates were tested for quinolone resistance and ESBL-producing using the disk diffusion method and double disk synergy (DDST confirmatory test. ESBL-producing strains were further evaluated for the blaCTX-M genes. The PCR method was used to show presence of plasmid-mediated quinolone resistance genes and the purified PCR products were sequenced. Eighty-seven ESBL-producing strains were identified by DDST confirmatory test and majority (70, 80.5% of which carried blaCTX-M genes including CTX-M-1 (60%, CTX-M-2 (42.9%, and CTX-M-9 (34.3%. Seventy-seven ESBL-producing K. pneumoniae isolates harbored PMQR genes, which mostly consisted of aac(6′-Ib-cr (70.1% and qnrB (46.0%, followed by qnrS (5.7%. Among the 77 PMQR-positive isolates, 27 (35.1% and 1 (1.3% carried 2 and 3 different PMQR genes, respectively. However, qnrA and qepA were not found in any isolate. Our results highlight high ESBL occurrence with CTX-M type and high frequency of plasmid-mediated quinolone resistance genes among ESBL-producing K. pneumoniae isolates in Kashan.

  11. 喹诺酮类药物的不良反应报告分析%Analysis of Quinolones Adverse Reaction Reports

    Institute of Scientific and Technical Information of China (English)

    王惠霞; 陆建平

    2012-01-01

      Objective:Explore the occurrence of adverse reactions of quinolones and clinical control measures.Method:A total of 27 cases of quinolone ADR reports collected in our hospital in 2009 were analyzed statistically in respect of patients age and sex,route of administration,drug varieties,organs or systems involved and the clinical manifestation.Result:Lesions of skin and its appendages were the most common damages of quinolone ADR.Conclusion:Importance should be attached to the reporting and monitoring of quinolone ADR reports in the clinic and reduce the incidence of adverse reactions.%  目的:探讨喹诺酮类药物不良反应(ADR)的发生情况与临床控制措施。方法:对笔者所在医院2011年1-12月上报的27例喹诺酮类药物 ADR 报告,按患者年龄、性别、药品类别、ADR 累及器官或系统及临床表现等进行统计、分析。结果:喹诺酮类抗菌药物药物的不良反应临床表现以皮肤及附件损害最多见。结论:临床应重视喹诺酮类药物的不良反应,加强 ADR 监测工作,促进临床合理用药,减少不良反应的发生。

  12. Serine-to-Asparagine Substitution in the GyrA Gene Leads to Quinolone Resistance in Moxifloxacin-Exposed Chlamydia pneumoniae

    OpenAIRE

    Rupp, Jan; Gebert, Andreas; Solbach, Werner; Maass, Matthias

    2005-01-01

    Quinolone resistance of Chlamydia pneumoniae has not been described previously. Serial subcultures of C. pneumoniae under increasing moxifloxacin concentrations (0.0125 to 6.4 mg/liter) resulted in a 256-fold MIC increase compared to moxifloxacin-naive strains. GyrA gene sequencing revealed a novel point mutation with a Ser→Asn substitution. Subcultures under rifalazil and macrolides did not alter the respective MICs.

  13. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Extended-Spectrum β -Lactamase-Producing Klebsiella pneumoniae Human Isolates in Iran.

    Science.gov (United States)

    Shams, Ehsaneh; Firoozeh, Farzaneh; Moniri, Rezvan; Zibaei, Mohammad

    2015-01-01

    The purpose of this study was to determine the prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR) genes (qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA) among ESBL-producing Klebsiella pneumoniae isolates in Kashan, Iran. A total of 185 K. pneumoniae isolates were tested for quinolone resistance and ESBL-producing using the disk diffusion method and double disk synergy (DDST) confirmatory test. ESBL-producing strains were further evaluated for the bla CTX-M genes. The PCR method was used to show presence of plasmid-mediated quinolone resistance genes and the purified PCR products were sequenced. Eighty-seven ESBL-producing strains were identified by DDST confirmatory test and majority (70, 80.5%) of which carried bla CTX-M genes including CTX-M-1 (60%), CTX-M-2 (42.9%), and CTX-M-9 (34.3%). Seventy-seven ESBL-producing K. pneumoniae isolates harbored PMQR genes, which mostly consisted of aac(6')-Ib-cr (70.1%) and qnrB (46.0%), followed by qnrS (5.7%). Among the 77 PMQR-positive isolates, 27 (35.1%) and 1 (1.3%) carried 2 and 3 different PMQR genes, respectively. However, qnrA and qepA were not found in any isolate. Our results highlight high ESBL occurrence with CTX-M type and high frequency of plasmid-mediated quinolone resistance genes among ESBL-producing K. pneumoniae isolates in Kashan. PMID:26618005

  14. Quinolone-resistant Escherichia coli isolated from birds of prey in Portugal are genetically distinct from those isolated from water environments and gulls in Portugal, Spain and Sweden.

    Science.gov (United States)

    Vredenburg, Jana; Varela, Ana Rita; Hasan, Badrul; Bertilsson, Stefan; Olsen, Björn; Narciso-da-Rocha, Carlos; Bonnedahl, Jonas; Stedt, Johan; Da Costa, Paulo Martins; Manaia, Célia M

    2014-04-01

    The influence of geographic distribution and type of habitat on the molecular epidemiology of ciprofloxacin resistant Escherichia coli was investigated. Ciprofloxacin resistant E. coli from wastewater, urban water with faecal contamination and faeces of gulls, pigeons and birds of prey, from Portugal, Spain and Sweden were compared based on multi-locus sequence typing (MLST) and quinolone resistance genetic determinants. Multi-locus sequence typing allowed the differentiation of E. coli lineages associated with birds of prey from those inhabiting gulls and waters. E. coli lineages of clinical relevance, such as the complex ST131, were detected in wastewater, streams and gulls in Portugal, Spain and Sweden. Quinolone resistance was due to gyrA and parC mutations, although distinct mutations were detected in birds of prey and in wastewater, streams and gulls isolates. These differences were correlated with specific MLST lineages, suggesting resistance inheritance. Among the plasmid-mediated quinolone resistance genes, only aac(6')-ib-cr and qnrS were detected in wastewater, streams and gulls isolates, but not in birds of prey. The horizontal transfer of the gene aac(6')-ib-cr could be inferred from its occurrence in different MLST lineages. PMID:24034690

  15. Functional analysis of spoT, relA and dksA genes on quinolone tolerance in Pseudomonas aeruginosa under nongrowing condition.

    Science.gov (United States)

    Viducic, Darija; Ono, Tsuneko; Murakami, Keiji; Susilowati, Heni; Kayama, Shizuo; Hirota, Katsuhiko; Miyake, Yoichiro

    2006-01-01

    To assess the contribution of ppGpp in antibiotic tolerance to quinolone in Pseudomonas aeruginosa, knockout mutants of the genes involved or linked with the stringent response, such as relA, spoT and dksA, were constructed and investigated for their antibiotic susceptibility to quinolones. The survival of the dksA and spoT mutants in the presence of 8 microg/ml of ofloxacin and 1 microg/ml of ciprofloxacin were shown to be approximately 20-180 and 10-40 times respectively, higher than the same for the wild type strain. The intracellular levels of ppGpp determined with high performance liquid chromatography (HPLC) demonstrated that spoT and dksA mutants possess higher basal levels of ppGpp. The data suggest that elevated basal levels of ppGpp may be responsible for rendering these mutants tolerant to quinolones and expand the importance of ppGpp as an antimicrobial target in P. aeruginosa.

  16. Anticancer drug-induced kidney disorders.

    Science.gov (United States)

    Kintzel, P E

    2001-01-01

    Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium

  17. Anti-Cancer Potential of a Novel SERM Ormeloxifene

    Science.gov (United States)

    Gara, Rishi Kumar; Sundram, Vasudha; Chauhan, Subhash C.; Jaggi, Meena

    2014-01-01

    Ormeloxifene is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that is used as an oral contraceptive. Recent studies have shown its potent anti-cancer activities in breast, head and neck, and chronic myeloid leukemia cells. Several in vivo and clinical studies have reported that ormeloxifene possesses an excellent therapeutic index and has been well-tolerated, without any haematological, biochemical or histopathological toxicity, even with chronic administration. A reasonably long period of time and an enormous financial commitment are required to develop a lead compound into a clinically approved anti-cancer drug. For these reasons and to circumvent these obstacles, ormeloxifene is a promising candidate on a fast track for the development or repurposing established drugs as anti-cancer agents for cancer treatment. The current review summarizes recent findings on ormeloxifene as an anti-cancer agent and future prospects of this clinically safe pharmacophore. PMID:23895678

  18. Enediyne anticancer antibiotic lidamycin: chemistry, biology and pharmacology.

    Science.gov (United States)

    Shao, Rong-guang; Zhen, Yong-su

    2008-02-01

    The enediyne antibiotics, the potent anticancer agents that contain diyne-ene functional groups, are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mechanism of action. Their anticancer activity is apparently due to their ability to damage DNA through radical-mediated hydrogen abstraction. The enediyne antibiotics show markedly cytotoxicities against cancers in vitro and in vivo. Lidamycin is a member of the enediyne anticancer antibiotic family. This review examines lidamycin with particular emphasis on the discovery, the biological properties and its structure-activity relationships. In addition, the possible mechanisms of action of lidamycin are described. Recent progress, particularly in the areas of biosynthesis, and immunoconjugates are highlighted. Finally, the pharmacological applications of lidamycin in cancer therapy and its potential use as anticancer agents are also discussed. PMID:18288918

  19. Production of Anti-Cancer Agent Using Microbial Biotransformation

    Directory of Open Access Journals (Sweden)

    Changhyun Roh

    2014-10-01

    Full Text Available Microbial biotransformation is a great model system to produce drugs and biologically active compounds. In this study, we elucidated the fermentation and production of an anti-cancer agent from a microbial process for regiospecific hydroxylation of resveratrol. Among the strains examined, a potent strain showed high regiospecific hydroxylation activity to produce piceatannol. In a 5 L (w/v 3 L jar fermentation, this wild type Streptomyces sp. in the batch system produced 205 mg of piceatannol (i.e., 60% yields from 342 mg of resveratrol in 20 h. Using the product, an in vitro anti-cancer study was performed against a human cancer cell line (HeLa. It showed that the biotransformed piceatannol possessed a significant anticancer activity. This result demonstrates that a biotransformation screening method might be of therapeutic interest with respect to the identification of anti-cancer drugs.

  20. Anticancer Compound Plumbagin and Its Molecular Targets: A Structural Insight into the Inhibitory Mechanisms Using Computational Approaches

    OpenAIRE

    Mohammad S Jamal; Shadma Parveen; Mohd A Beg; Mohd Suhail; Chaudhary, Adeel G. A.; Damanhouri, Ghazi A.; Abuzenadah, Adel M; Mohd Rehan

    2014-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naphthoquinone derivative from the roots of plant Plumbago zeylanica and belongs to one of the largest and diverse groups of plant metabolites. The anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin exerts inhibitory effects on multiple cancer-signaling proteins, however, the binding mode and the molecular interactions have not yet been elucidated for most of...

  1. [Susceptibility of clinically-isolated bacteria strains to respiratory quinolones and evaluation of antimicrobial agent efficacy by Monte Carlo simulation].

    Science.gov (United States)

    Kosaka, Tadashi; Yamada, Yukiji; Kimura, Takeshi; Kodama, Mai; Fujitomo, Yumiko; Masaki, Nakanishi; Toshiaki, Komori; Keisuke, Shikata; Fujita, Naohisa

    2016-02-01

    Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients' renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n = number of strains) [Streptococcus pneumoniae (n = 15), Streptococcus pyogenes (n = 14), Streptococcus agalactiae (n = 19), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24), Escherichia coli (n = 35), Haemophilus influenzae (n = 17), Klebsiella pneumoniae (n = 14), Pseudomonas aeruginosa (n = 31), and Moraxella catarrhalis (n = 11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, > 16, and 8 µg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being > 16, 16, 1, and 16 µg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration-time curve divided by the MIC₉₀ (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also

  2. The Extraction, Anticancer Effect, Bioavailability, and Nanotechnology of Baicalin

    Science.gov (United States)

    Moore, Ondrea A.; Gao, Ying; Chen, Allen Y.; Brittain, Ross; Chen, Yi Charlie

    2016-01-01

    The dried root of Baikal skullcap (Scutellaria baicalensis) has been historically and widely used in traditional Eastern medicine. Modern science proved that baicalin is the major bioactive responsible for the physiological activity of Baikal skullcap. Baicalin, a flavonoid found in several species in the genus Scutellaria, has been regarded as a potent anticancer agent. In this review, we present the main extraction methods, anticancer activity and bioavailability of baicalin. Besides, the utilization of nanotechnology to improve the bioavailability of baicalin is also mentioned.

  3. Anti-cancer potential of South Asian plants

    OpenAIRE

    Rahman, Mohammad Mijanur; Khan, Md Asaduzzaman

    2013-01-01

    Phyto-chemicals are increasingly being used in the treatment of cancer because of their availability, potential anti-cancer activity with less adverse effects when compared with chemotherapy. The variation of climate and geography in South Asian countries provides a nursing environment for the growth of versatile plant species, that are repeatedly drawing attention of the scientific community. In this review, we have focused on the anti-cancer potential of thirty plants, which are commonly fo...

  4. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Dmitry L. Aminin

    2015-03-01

    Full Text Available Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata. They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor, Akt (protein kinase B, ERK (extracellular signal-regulated kinases, FAK (focal adhesion kinase, MMP-9 (matrix metalloproteinase-9 and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

  5. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou

    2012-01-01

    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.

  6. Indigofera suffruticosa: An Alternative Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Jeymesson Raphael Cardoso Vieira

    2007-01-01

    Full Text Available Indigofera suffruticosa Mill (Fabeceae occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53% and maceration (62.62% against sarcoma 180 in mice at a dose of 50 mg kg−1 (intraperitoneally, based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

  7. Peptidomimetics and metalloprotease inhibitors as anticancer drugs

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.

  8. Calcium channel as a potential anticancer agent.

    Science.gov (United States)

    Kriazhev, L

    2009-11-01

    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

  9. MECHANOMAGNETIC REACTOR FOR ACTIVATION OF ANTICANCER DRUGS

    Directory of Open Access Journals (Sweden)

    Orel V. E.

    2014-02-01

    Full Text Available Mechanomagnetochemical activation can increase the concentration of paramagnetic centers (free radicals in the anticancer drug, for example, doxorubicin that enables to influence its magnetic properties under external electromagnetic field and improve its magnetic sensitivity and antitumor activity. The principles of design and operation of mechanomagnetic reactor for implementation of this technology which includes mechanomagnetochemical activation and electromagnetic radiation of the drug are described in the paper. The methods of vibration magnetometry, electron paramagnetic resonance spectroscopy and high-performance liquid chromatography were used for studying of doxorubicin mechanomagnetic activation effects. The studies have shown that a generator of sinusoidal electromagnetic wave, working chambers from caprolactam, fluoroplastic or organic materials with metal inserts and working bodies made from steel or agate depending on the required doxorubicin magnetic properties are expedient to use in the designed mechanomagnic reactor. Under influence of mechanomagnetochemical activation doxorubicin, which is diamagnetic, acquires the properties of paramagnetic without changing g-factors in the spectra of electron paramagnetic resonance. Mechanomagnetochemical activation of doxorubicin satisfies pharmacopoeia condi tions according to the results of liquid chromatography that points on perspective of this method using in technology of tumor therapy with nanosized structures and external electromagnetic radiation.

  10. Peptidomimetics and metalloprotease inhibitors as anticancer drugs

    Institute of Scientific and Technical Information of China (English)

    SU Li; XU WenFang

    2009-01-01

    Peptidomimetics with three types, as the structural or functional mimetica of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetica of high bioectivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-baeed drugs, and many proteasee and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetice as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peplldomimetic inhibitora of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinaees play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitora based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.

  11. Sensitization for Anticancer Drug-Induced Apoptosis by Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2005-02-01

    Full Text Available We previously described that betulinic acid (BetA, a naturally occurring pentacyclic triterpenoid, induces apoptosis in tumor cells through the mitochondrial pathway. Here, for the first time, we provide evidence that BetA cooperated with anticancer drugs to induce apoptosis and to inhibit clonogenic survival of tumor cells. Combined treatment with BetA and anticancer drugs acted in concert to induce loss of mitochondrial membrane potential and the release of cytochrome c and Smac from mitochondria, resulting in activation of caspases and apoptosis. Overexpression of Bcl-2, which blocked mitochondrial perturbations, also inhibited the cooperative effect of BetA and anticancer drugs, indicating that cooperative interaction involved the mitochondrial pathway. Notably, cooperation of BetA and anticancer drugs was found for various cytotoxic compounds with different modes of action (e.g., doxorubicin, cisplatin, Taxol, VP16, or actinomycin D. Importantly, BetA and anticancer drugs cooperated to induce apoptosis in different tumor cell lines, including p53 mutant cells, and also in primary tumor cells, but not in human fibroblasts indicating some tumor specificity. These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation.

  12. Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-10-01

    Full Text Available Yuanyuan Wang, Xin Qi, Dehai Li, Tianjiao Zhu, Xiaomei Mo, Jing LiKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of ChinaAbstract: Since the first anthracycline was discovered, many other related compounds have been studied in order to overcome its defects and improve efficacy. In the present paper, we investigated the anticancer effects of a new anthracycline, aspergiolide A (ASP-A, from a marine-derived fungus in vitro and in vivo, and we evaluated the absorption, distribution, metabolism, and toxicity drug properties in early drug development. We found that ASP-A had activity against topoisomerase II that was comparable to adriamycin. ASP-A decreased the growth of various human cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase-dependent pathway. The anticancer efficacy of ASP-A on the growth of hepatocellular carcinoma xenografts was further assessed in vivo. Results showed that, compared with the vehicle group, ASP-A exhibited significant anticancer activity with less loss of body weight. A pharmacokinetics and tissue distribution study revealed that ASP-A was rapidly cleared in a first order reaction kinetics manner, and was enriched in cancer tissue. The maximal tolerable dose (MTD of ASP-A was more than 400 mg/kg, and ASP-A was not considered to be potentially genotoxic or cardiotoxic, as no significant increase of micronucleus rates or inhibition of the hERG channel was seen. Finally, an uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells, and ASP-A was shown to be absorbed through the active transport pathway. Altogether, these results indicate that ASP-A has anticancer activity targeting topoisomerase II, with a similar structure and mechanism to adriamycin, but with much lower toxicity. Nonetheless, further molecular structure optimization is necessary.Keywords: aspergiolide A, anticancer

  13. Electrogenerated chemiluminescence: An oxidative-reductive mechanism between quinolone antibiotics and tris(2,2'-bipyridyl)ruthenium(II)

    Energy Technology Data Exchange (ETDEWEB)

    Burkhead, Matthew S.; Wang, Heeyoung; Fallet, Marcel [Department of Chemistry, Creighton University, Omaha, NE 68178 (United States); Gross, Erin M. [Department of Chemistry, Creighton University, Omaha, NE 68178 (United States)], E-mail: eringross@creighton.edu

    2008-04-21

    The cyclic voltammetry and electrogenerated chemiluminescent (ECL) reactions of a series of quinolone and fluoroquinolone antibiotics were investigated in a flow injection analysis (FIA) system. 7-Piperazinyl fluoroquinolone antibiotics were found to participate as a coreactant in an oxidative-reductive ECL mechanism with tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy){sub 3}{sup 2+}) as the luminescent reagent. The reaction mechanism was investigated in order to understand and optimize the processes leading to light emission. The optimal conditions included a solution pH {approx}7 at a flow rate of 3.0 mL min{sup -1} with no added organic modifier and application of 1.2 V vs. a Pt quasi-reference electrode (QRE). Fluoroquinolones containing a tertiary distal nitrogen on the piperazine ring, such as enrofloxacin and ofloxacin, reacted to produce more intense ECL than those with a secondary nitrogen, such as ciprofloxacin and norfloxacin. The method linear range, precision, detection limits, and sensitivity for the detection of enrofloxacin and ciprofloxacin were compared to that of tripropylamine. The method was applied to the determination of the ciprofloxacin content in a pharmaceutical preparation. The assay is discussed in terms of its analytical figures of merit, ease of use, speed, accuracy and application to pharmaceutical samples.

  14. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone.

    Science.gov (United States)

    Lawres, Lauren A; Garg, Aprajita; Kumar, Vidya; Bruzual, Igor; Forquer, Isaac P; Renard, Isaline; Virji, Azan Z; Boulard, Pierre; Rodriguez, Eduardo X; Allen, Alexander J; Pou, Sovitj; Wegmann, Keith W; Winter, Rolf W; Nilsen, Aaron; Mao, Jialing; Preston, Douglas A; Belperron, Alexia A; Bockenstedt, Linda K; Hinrichs, David J; Riscoe, Michael K; Doggett, J Stone; Ben Mamoun, Choukri

    2016-06-27

    Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis. PMID:27270894

  15. Occurrence of sulfonamide-, tetracycline-, plasmid-mediated quinolone- and macrolide-resistance genes in livestock feedlots in Northern China.

    Science.gov (United States)

    Mu, Quanhua; Li, Jin; Sun, Yingxue; Mao, Daqing; Wang, Qing; Luo, Yi

    2015-05-01

    Antibiotic resistance genes (ARGs) in livestock feedlots deserve attention because they are prone to transfer to human pathogens and thus pose threats to human health. In this study, the occurrence of 21 ARGs, including tetracycline (tet)-, sulfonamide (sul)-, plasmid-mediated quinolone (PMQR)- and macrolide-resistance (erm) genes were investigated in feces and adjacent soils from chicken, swine, and cattle feedlots in Northern China. PMQR and sul ARGs were the most prevalent and account for over 90.0 % of the total ARGs in fecal samples. Specifically, PMQR genes were the most prevalent, accounting for 59.6 % of the total ARGs, followed by sul ARGs (34.2 %). The percentage of tet ARGs was 3.4 %, and erm ARGs accounted for only 1.9 %. Prevalence of PMQR and sul ARGs was also found in swine and cattle feces. The overall trend of ARG concentrations in feces of different feeding animals was chicken > swine > beef cattle in the studied area. In soils, sul ARGs had the highest concentration and account for 71.1 to 80.2 % of the total ARGs, which is possibly due to the widely distributed molecular carriers (i.e., class one integrons), facilitating sul ARG propagation. Overall, this study provides integrated profiles of various types of ARGs in livestock feedlots and thus provides a reference for the management of antibiotic use in livestock farming. PMID:25475616

  16. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-01

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed.

  17. Coexistence of plasmid-mediated quinolone resistance determinants and AmpC-Beta-Lactamases in Escherichia coli strains in Egypt.

    Science.gov (United States)

    Abd El-Aziz, N K; Gharib, A A

    2015-01-01

    Three kinds of plasmid—mediated quinolone resistance (PMQR) determinants (qnr genes, qepA and aac(6')—Ib—cr) have been discovered and shown to be widely distributed among clinical isolates. To characterize the prevalence of PMQR determinants among AmpC—producing E. coli strains in food—producing animals and animal by—products in Egypt, twenty—nine E. coli strains were tested for their susceptibilities to antimicrobials and screened for PMQR determinants and AmpC Beta lactamases using PCR and plasmid profiling. It was found that qnr genes being detected alone or in combination with qepA or aac(6')—Ib—cr genes in 11 (37.9%) strains comprising 9 for qnrA and only one for both qnrB and qnrS. Moreover, qepA and aac(6')—Ib—cr were detected in 41.38% and 3.45% of E. coli strains, respectively. The ampC β—lactamase genes were detected in 75.86 % of all strains and in 100% and 53.3% of the PMQR determinant—positive and negative strains, respectively. In several cases, plasmid profiling of E. coli strains exhibiting the coexistence of both PMQR determinants and ampC genes on a single plasmid as a first report in Egypt that may contribute to rapid spread and increase in bacterial resistance, which is important to public health concern. PMID:26475385

  18. A Review for the Analysis of Antidepressant, Antiepileptic and Quinolone Type Drugs in Pharmaceuticals and Environmental Samples.

    Science.gov (United States)

    Rani, Susheela; Malik, Ashok Kumar; Kaur, Ramandeep; Kaur, Ripneel

    2016-09-01

    The analysis of drugs in various biological fluids is an important criterion for the determination of the physiological performance of a drug. After sampling of the biological fluid, the next step in the analytical process is sample preparation. Sample preparation is essential for isolation of desired components from complex biological matrices and greatly influences their reliable and accurate determination. The complexity of biological fluids adds to the challenge of direct determination of the drug by chromatographic analysis, therefore demanding a sample preparation step that is often time consuming, tedious and frequently overlooked. However, direct online injection methods offer the advantage of reducing sample preparation steps and enabling effective pre-concentration and clean-up of biological fluids. These procedures can be automated and therefore reduce the requirements for handling potentially infectious biomaterial, improve reproducibility, and minimize sample manipulations and potential contamination. This review is focused on the discovery and development of high-performance liquid chromatography (HPLC) and gas chromatography (GC) with different detectors. The drugs covered in this review are antiepileptics, antidepressant (AD), and quinolones. The application of these methods for determination of these drugs in biological, environmental and pharmaceutical samples has also been discussed. PMID:26939618

  19. Analysis of damaged DNA / proteins interactions: Methodological optimizations and applications to DNA lesions induced by platinum anticancer drugs; Analyse des interactions ADN lese / proteines: Optimisations methodologiques et applications aux dommages de l'ADN engendres par les derives du platine

    Energy Technology Data Exchange (ETDEWEB)

    Bounaix Morand du Puch, Ch

    2010-10-15

    DNA lesions contribute to the alteration of DNA structure, thereby inhibiting essential cellular processes. Such alterations may be beneficial for chemotherapies, for example in the case of platinum anticancer agents. They generate bulky adducts that, if not repaired, ultimately cause apoptosis. A better understanding of the biological response to such molecules can be obtained through the study of proteins that directly interact with the damages. These proteins constitute the DNA lesions interactome. This thesis presents the development of tools aiming at increasing the list of platinum adduct-associated proteins. Firstly, we designed a ligand fishing system made of damaged plasmids immobilized onto magnetic beads. Three platinum drugs were selected for our study: cisplatin, oxali-platin and satra-platin. Following exposure of the trap to nuclear extracts from HeLa cancer cells and identification of retained proteins by proteomics, we obtained already known candidates (HMGB1, hUBF, FACT complex) but also 29 new members of the platinated-DNA interactome. Among them, we noted the presence of PNUTS, TOX4 and WDR82, which associate to form the recently-discovered PTW/PP complex. Their capture was then confirmed with a second model, namely breast cancer cell line MDA MB 231, and the biological consequences of such an interaction now need to be elucidated. Secondly, we adapted a SPRi bio-chip to the study of platinum-damaged DNA/proteins interactions. Affinity of HMGB1 and newly characterized TOX4 for adducts generated by our three platinum drugs could be validated thanks to the bio-chip. Finally, we used our tools, as well as analytical chemistry and biochemistry methods, to evaluate the role of DDB2 (a factor involved in the recognition of UV-induced lesions) in the repair of cisplatin adducts. Our experiments using MDA MB 231 cells differentially expressing DDB2 showed that this protein is not responsible for the repair of platinum damages. Instead, it appears to act

  20. Endophytic fungi: novel sources of anticancer lead molecules.

    Science.gov (United States)

    Chandra, Sheela

    2012-07-01

    Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe